小鼠胚胎发育时期心肌细胞电压门控性钠通道的分子和功能性改变
|
摘要
背景：心律失常是临床上常见的疾病。其机制较为复杂。从根本上说,心肌细胞各种离子通道表达或功能的异常是形成各种心律失常最重要的病理生理基础。
钠通道在心肌细胞动作电位起始与传播中起着重要的作用。近年来研究证实,钠通道门控特征改变是形成某些长QT综合征、Brugada's syndrome和一些遗传性心脏传导疾病的根本原因。并且,在一些获得性心脏疾病如心肌缺血和心衰中,人们也发现钠通道门控特征发生了变化。另外,在患病心脏中,一些细胞内调节的信号途径如cAMP依赖的蛋白激酶A途径也发生了变化。
改善衰竭心脏功能的一个实验性策略即是进行细胞移植。已有许多研究者正尝试着应用胚胎心肌、胚胎心脏前体细胞和骨髓干细胞进行移植研究。这些创新方法由于缺乏对正常心肌分化尤其是胚胎发育阶段的了解而受到阻碍。因此,研究胚胎心脏中Na+通道的门控特征变化及其调控,从病理生理和治疗学上来说都是具有十分重要的意义。
目的：应用胚胎小鼠心室肌细胞,观察不同胚胎发育时期钠通道门控特征的变化；检测胚胎心脏中钠通道各亚单位的表达性改变,以探讨与功能变化相关的分子机制。
方法：急性分离早期(胎龄10.5 d)和晚期(胎龄17.5 d)胚胎小鼠心脏,采用胶原酶Ⅱ,分离获得单个的心室肌细胞,并置于CO2培养箱中培养24-48h后进行电生理记录。用标准的全细胞膜片钳技术,记录胚胎小鼠心室肌细胞的钠电流；利用RT-PCR技术检测了胚胎心脏中钠通道六种α亚单位(Nav1.1-Nav1.6)和三种β亚单位(Navβ1-Navβ3)的表达量。
结果：通过酶解法得到的胚胎小鼠心室肌细胞能够记录到相应的INa电流,表明其具有良好的细胞电生理特性。
1.不同发育时期INa电流密度的变化：晚期心室肌细胞与早期心室肌细胞相比,峰INa电流密度在从-60至+20 mV的刺激电压范围内明显增大。在-30 mV处,INa电流密度从早期的-88.1±8.0 pA/pF (n=8)增大为晚期的-287.9±9.7pA/pF(n=11,P<0.01)。
2.不同发育时期INa电流激活特征的变化：早期心室肌细胞与晚期细胞的激活特征相似。两种心肌细胞的半数激活电压(Va:-46.1±3.4 mV EDS vs.-47.0±3.4 mV LDS, P>0.05)和斜率(k:5.5±0.4 mV EDS vs.5.8±0.7 mV LDS, P>0.05)较为接近。另外,两种细胞在-60至0 mV范围内,其INa电流达峰时间相似。
3.不同发育时期INa电流失活特征的变化：与早期心肌细胞(Vi:-71.6±2.4mV EDS, P<0.01)相比,晚期心室肌细胞(Vi:-82.7±4.4 mV LDS P<0.01)的半数失活电压明显向负电位方向偏移。而斜率并没有显著性差异(k:7.2±0.7 mV EDS vs.6.5±0.9 mV LDS, P>0.05).另外,在-30 mV电压处,钠电流的失活相均符合双指数拟和,都含有一个快失活成分和慢失活成分。两种细胞的快、慢失活时间相近。而就两种失活成分的相对幅度来说,晚期心肌细胞较之早期细胞具有更大幅度的快失活成分和更小幅度的慢失活成分。
4.不同发育时期INa电流复活特征的变化：与失活特征相似,INa电流复活过程也包含有快、慢两种成分。与早期心室肌细胞相比,晚期心肌细胞的快慢时间常数均表现为明显减小。早期心室肌细胞INa电流的两种时间常数分别为τf=7.5±0.5ms和τs=198.6±12.3 ms；晚期心室肌细胞INa电流的两种时间常数分别为τf=5.5±0.4 ms和τs=122.5±4.5 ms。
5.不同发育时期钠通道α亚单位和p亚单位表达量的改变：在钠通道α亚单位中,Nav1.1、Nav1.2和Nav1.3的表达量在胚胎心脏中始终是缺乏或处于低表达水平。Nav1.4、Nav1.5和Nav1.6的表达量随着小鼠胚胎发育而明显增大。另外,三种钠通道p亚单位(Navβ1、Navβ2、Navβ3)的表达量也是随着发育明显上调。
6.不同发育时期总INa电流对河豚毒(TTX)的敏感性：为了比较早期、晚期心肌细胞总钠电流对TTX敏感性的不同,我们分析了TTX抑制早期心肌细胞和晚期心肌细胞总INa电流的剂量-浓度反应关系。结果发现,在这两种心肌细胞中,TTX均以浓度依赖性方式抑制了总INa电流。采用Hill公式拟和,得到相应半数抑制浓度IC50值为5.2μM(早期心肌细胞)和6.6μM(晚期心肌细胞)。
结论：在小鼠胚胎发育时期,心脏钠通道存在着显著性功能特征改变；与功能变化相对应,钠通道各亚单位的表达也受到了胚胎发育过程的紧密调节；这些发现证实了电压门控性钠通道在心脏发育过程中起着一定的生理作用。
Background:Cardiac arrhythmia is common in the clinical practice, and its mechanism is complex. Fundamentally, the abnormalities of expression and function of the membrane ion channels can contribute to the development of cardiac arrhythmias.
Na+ channel plays a key role in the generation and conduction of action potential in the heart. It has been showed that altered Na+ channel gating might underlie multiple cardiac diseases, such as long QT syndrome (LQTS), the Brugada syndrome and some inheritable cardiac conduction disorders. Na+ channel gating is altered in acquired diseases such as cardiac ischemia and heart failure. In addition, some signaling pathways that regulate Na+ channel function are altered in the diseased heart, such as cAMP-dependent protein kinase A (PKA).
An experimental strategy to improve cardiac function in failing hearts is cell transplant. Some investigator has attempted to engraft fetal cardiomyocytes, and bone marrow stem cell. However, progress in this approach is hampered by lack of knowledge about normal differentiation of cardiomyocytes especially at embryonic stage. Thus, it would be of great interest to determine the developmental changes in gating properties of Na+ channel from a pathophysiological and therapeutic standpoint.
Objective:To study the developmental changes in gating properties of Na+ channel during embryogenesis and to determine the changes in Na+ channel subunits expression that might be associated with functional changes.
Methods:Single ventricular myocytes from embryos of early developmental stage (10.5 days postcoitum) and late developmental stage (17.5 days postcoitum) were obtained by enzymatic dissociation method and kept in the incubator for 24-48 hours until use. Whole-cell voltage-clamp technique was used to record Na+ currents in ventricular myocytes of early (EDS) and late (LDS) developmental stages in embryonic mice。Additionally, RT-PCR was performed to determine the transcripts of six Na+ channel a subunits (Nav1.1-Nav1.6) and threeβsubunits (Navβ1-Navβ3)。
Results:Na+ current could be recorded in the isolated ventricular myocytes of both developmental stages, which indicated these myocytes had satisfactory electrophysiological properties.
1. Developmental changes in peak INa current density:Peak Na+ current density was significantly larger in LDS cells (-60 to +20 mV) than in EDS cells (P<0.01). Na+ current density at -30 mV increased significantly from -88.1±8.0 pA/pF (n=8) in EDS to -287.9±9.7 pA/pF (n=11,P<0.01) in LDS.
2. Developmental changes in activation properties of Na+ channels:The voltage dependence of activation in both cell types were similar. There was no significant difference in the voltage of half activation (Va) and slope factor (k) between EDS and LDS myocytes (Va:-46.1±3.4 mV EDS vs.-47.0±3.4 mV LDS, P>0.05; k:5.5±0.4 mV EDS vs.5.8±0.7 mV LDS, P>0.05). In addition, the time-to-peaks in both cell types were similar at potentials over -60 to 0 mV.
3. Developmental changes in inactivation properties of Na+ channels:The voltage of half inactivation (V;) was shifted to more negative potentials in LDS than EDS cells (Vi:-82.7±4.4 mV LDS vs.-71.6±2.4 mV EDS, P<0.01). K values for EDS and LDS cells were not significantly different (k:7.2±0.7 mV EDS vs.6.5±0.9 mV LDS, P>0.05).
In addition, the time course of inactivation at a test potential of-30 mV was well described by a bi-exponential fit in both cell types, containing a large fast component and a small slow component. Both the time constants of Na+ channel inactivation in both cell types were similar. But LDS myocytes had significantly larger amplitude of fast (Af) inactivation component and smaller amplitude of slow (As) inactivation component than EDS myocytes.
4. Developmental changes in recovery properties of Na+ channels:Similarly, the time course of recovery from inactivation in both cell types also included a large fast component and a small slow component. The fast (if) and slow (τs) time constants for Na+ channel recovery were significantly smaller in LDS (τf:5.5±0.4 ms LDS vs. 7.5±0.5 ms EDS, P<0.01;τs:122.5±4.5 ms LDS vs.198.6±12.3 ms EDS, P<0.01) than in EDS cells.
5. Expression of Na+ channel a subunits andβsubunits in embryonic cardiomyocytes:Transcripts of Navl.1, Nav1.2 and Nav1.3 were absent or present at very low levels in embryonic hearts. The amount of Nav1.4, Nav1.5 and Nav1.6 mRNA were increased with age during embryogenesis. Additionally, three Na+ channel 3 subunits (Navβ1-Navβ3) were upregulated during embryogenesis.
6. Sensitivity of total Na+ currents to TTX in EDS and LDS cardiocytes:To determine the sensitivity of total Na+ current in both embryonic cardiomyocytes types, we analyzed the relationship between the dose of TTX and the blocking effect of TTX on total INa·Total Na+ currents were decreased in a dose-dependent manner by TTX in both myocyte types. Fitting the dose-response relationship with Hill equation yielded an IC50 of 5.2μM (EDS) and 6.6μM (LDS).
Conclusions:These results suggest significantly functional changes in Na+ channels occur in cardiomyocytes of mouse embryo and that different Na+ channel subunits genes are strongly regulated during embryogenesis, and further support a physiological role for voltage-gated Na+ channels during heart development.
钠通道在心肌细胞动作电位起始与传播中起着重要的作用。近年来研究证实,钠通道门控特征改变是形成某些长QT综合征、Brugada's syndrome和一些遗传性心脏传导疾病的根本原因。并且,在一些获得性心脏疾病如心肌缺血和心衰中,人们也发现钠通道门控特征发生了变化。另外,在患病心脏中,一些细胞内调节的信号途径如cAMP依赖的蛋白激酶A途径也发生了变化。
改善衰竭心脏功能的一个实验性策略即是进行细胞移植。已有许多研究者正尝试着应用胚胎心肌、胚胎心脏前体细胞和骨髓干细胞进行移植研究。这些创新方法由于缺乏对正常心肌分化尤其是胚胎发育阶段的了解而受到阻碍。因此,研究胚胎心脏中Na+通道的门控特征变化及其调控,从病理生理和治疗学上来说都是具有十分重要的意义。
目的：应用胚胎小鼠心室肌细胞,观察不同胚胎发育时期钠通道门控特征的变化；检测胚胎心脏中钠通道各亚单位的表达性改变,以探讨与功能变化相关的分子机制。
方法：急性分离早期(胎龄10.5 d)和晚期(胎龄17.5 d)胚胎小鼠心脏,采用胶原酶Ⅱ,分离获得单个的心室肌细胞,并置于CO2培养箱中培养24-48h后进行电生理记录。用标准的全细胞膜片钳技术,记录胚胎小鼠心室肌细胞的钠电流；利用RT-PCR技术检测了胚胎心脏中钠通道六种α亚单位(Nav1.1-Nav1.6)和三种β亚单位(Navβ1-Navβ3)的表达量。
结果：通过酶解法得到的胚胎小鼠心室肌细胞能够记录到相应的INa电流,表明其具有良好的细胞电生理特性。
1.不同发育时期INa电流密度的变化：晚期心室肌细胞与早期心室肌细胞相比,峰INa电流密度在从-60至+20 mV的刺激电压范围内明显增大。在-30 mV处,INa电流密度从早期的-88.1±8.0 pA/pF (n=8)增大为晚期的-287.9±9.7pA/pF(n=11,P<0.01)。
2.不同发育时期INa电流激活特征的变化：早期心室肌细胞与晚期细胞的激活特征相似。两种心肌细胞的半数激活电压(Va:-46.1±3.4 mV EDS vs.-47.0±3.4 mV LDS, P>0.05)和斜率(k:5.5±0.4 mV EDS vs.5.8±0.7 mV LDS, P>0.05)较为接近。另外,两种细胞在-60至0 mV范围内,其INa电流达峰时间相似。
3.不同发育时期INa电流失活特征的变化：与早期心肌细胞(Vi:-71.6±2.4mV EDS, P<0.01)相比,晚期心室肌细胞(Vi:-82.7±4.4 mV LDS P<0.01)的半数失活电压明显向负电位方向偏移。而斜率并没有显著性差异(k:7.2±0.7 mV EDS vs.6.5±0.9 mV LDS, P>0.05).另外,在-30 mV电压处,钠电流的失活相均符合双指数拟和,都含有一个快失活成分和慢失活成分。两种细胞的快、慢失活时间相近。而就两种失活成分的相对幅度来说,晚期心肌细胞较之早期细胞具有更大幅度的快失活成分和更小幅度的慢失活成分。
4.不同发育时期INa电流复活特征的变化：与失活特征相似,INa电流复活过程也包含有快、慢两种成分。与早期心室肌细胞相比,晚期心肌细胞的快慢时间常数均表现为明显减小。早期心室肌细胞INa电流的两种时间常数分别为τf=7.5±0.5ms和τs=198.6±12.3 ms；晚期心室肌细胞INa电流的两种时间常数分别为τf=5.5±0.4 ms和τs=122.5±4.5 ms。
5.不同发育时期钠通道α亚单位和p亚单位表达量的改变：在钠通道α亚单位中,Nav1.1、Nav1.2和Nav1.3的表达量在胚胎心脏中始终是缺乏或处于低表达水平。Nav1.4、Nav1.5和Nav1.6的表达量随着小鼠胚胎发育而明显增大。另外,三种钠通道p亚单位(Navβ1、Navβ2、Navβ3)的表达量也是随着发育明显上调。
6.不同发育时期总INa电流对河豚毒(TTX)的敏感性：为了比较早期、晚期心肌细胞总钠电流对TTX敏感性的不同,我们分析了TTX抑制早期心肌细胞和晚期心肌细胞总INa电流的剂量-浓度反应关系。结果发现,在这两种心肌细胞中,TTX均以浓度依赖性方式抑制了总INa电流。采用Hill公式拟和,得到相应半数抑制浓度IC50值为5.2μM(早期心肌细胞)和6.6μM(晚期心肌细胞)。
结论：在小鼠胚胎发育时期,心脏钠通道存在着显著性功能特征改变；与功能变化相对应,钠通道各亚单位的表达也受到了胚胎发育过程的紧密调节；这些发现证实了电压门控性钠通道在心脏发育过程中起着一定的生理作用。
Background:Cardiac arrhythmia is common in the clinical practice, and its mechanism is complex. Fundamentally, the abnormalities of expression and function of the membrane ion channels can contribute to the development of cardiac arrhythmias.
Na+ channel plays a key role in the generation and conduction of action potential in the heart. It has been showed that altered Na+ channel gating might underlie multiple cardiac diseases, such as long QT syndrome (LQTS), the Brugada syndrome and some inheritable cardiac conduction disorders. Na+ channel gating is altered in acquired diseases such as cardiac ischemia and heart failure. In addition, some signaling pathways that regulate Na+ channel function are altered in the diseased heart, such as cAMP-dependent protein kinase A (PKA).
An experimental strategy to improve cardiac function in failing hearts is cell transplant. Some investigator has attempted to engraft fetal cardiomyocytes, and bone marrow stem cell. However, progress in this approach is hampered by lack of knowledge about normal differentiation of cardiomyocytes especially at embryonic stage. Thus, it would be of great interest to determine the developmental changes in gating properties of Na+ channel from a pathophysiological and therapeutic standpoint.
Objective:To study the developmental changes in gating properties of Na+ channel during embryogenesis and to determine the changes in Na+ channel subunits expression that might be associated with functional changes.
Methods:Single ventricular myocytes from embryos of early developmental stage (10.5 days postcoitum) and late developmental stage (17.5 days postcoitum) were obtained by enzymatic dissociation method and kept in the incubator for 24-48 hours until use. Whole-cell voltage-clamp technique was used to record Na+ currents in ventricular myocytes of early (EDS) and late (LDS) developmental stages in embryonic mice。Additionally, RT-PCR was performed to determine the transcripts of six Na+ channel a subunits (Nav1.1-Nav1.6) and threeβsubunits (Navβ1-Navβ3)。
Results:Na+ current could be recorded in the isolated ventricular myocytes of both developmental stages, which indicated these myocytes had satisfactory electrophysiological properties.
1. Developmental changes in peak INa current density:Peak Na+ current density was significantly larger in LDS cells (-60 to +20 mV) than in EDS cells (P<0.01). Na+ current density at -30 mV increased significantly from -88.1±8.0 pA/pF (n=8) in EDS to -287.9±9.7 pA/pF (n=11,P<0.01) in LDS.
2. Developmental changes in activation properties of Na+ channels:The voltage dependence of activation in both cell types were similar. There was no significant difference in the voltage of half activation (Va) and slope factor (k) between EDS and LDS myocytes (Va:-46.1±3.4 mV EDS vs.-47.0±3.4 mV LDS, P>0.05; k:5.5±0.4 mV EDS vs.5.8±0.7 mV LDS, P>0.05). In addition, the time-to-peaks in both cell types were similar at potentials over -60 to 0 mV.
3. Developmental changes in inactivation properties of Na+ channels:The voltage of half inactivation (V;) was shifted to more negative potentials in LDS than EDS cells (Vi:-82.7±4.4 mV LDS vs.-71.6±2.4 mV EDS, P<0.01). K values for EDS and LDS cells were not significantly different (k:7.2±0.7 mV EDS vs.6.5±0.9 mV LDS, P>0.05).
In addition, the time course of inactivation at a test potential of-30 mV was well described by a bi-exponential fit in both cell types, containing a large fast component and a small slow component. Both the time constants of Na+ channel inactivation in both cell types were similar. But LDS myocytes had significantly larger amplitude of fast (Af) inactivation component and smaller amplitude of slow (As) inactivation component than EDS myocytes.
4. Developmental changes in recovery properties of Na+ channels:Similarly, the time course of recovery from inactivation in both cell types also included a large fast component and a small slow component. The fast (if) and slow (τs) time constants for Na+ channel recovery were significantly smaller in LDS (τf:5.5±0.4 ms LDS vs. 7.5±0.5 ms EDS, P<0.01;τs:122.5±4.5 ms LDS vs.198.6±12.3 ms EDS, P<0.01) than in EDS cells.
5. Expression of Na+ channel a subunits andβsubunits in embryonic cardiomyocytes:Transcripts of Navl.1, Nav1.2 and Nav1.3 were absent or present at very low levels in embryonic hearts. The amount of Nav1.4, Nav1.5 and Nav1.6 mRNA were increased with age during embryogenesis. Additionally, three Na+ channel 3 subunits (Navβ1-Navβ3) were upregulated during embryogenesis.
6. Sensitivity of total Na+ currents to TTX in EDS and LDS cardiocytes:To determine the sensitivity of total Na+ current in both embryonic cardiomyocytes types, we analyzed the relationship between the dose of TTX and the blocking effect of TTX on total INa·Total Na+ currents were decreased in a dose-dependent manner by TTX in both myocyte types. Fitting the dose-response relationship with Hill equation yielded an IC50 of 5.2μM (EDS) and 6.6μM (LDS).
Conclusions:These results suggest significantly functional changes in Na+ channels occur in cardiomyocytes of mouse embryo and that different Na+ channel subunits genes are strongly regulated during embryogenesis, and further support a physiological role for voltage-gated Na+ channels during heart development.
引文
[1]Wichter, T., E. Schulze-Bahr, L. Eckardt, M. Paul, B. Levkau, M. Meyborg, M. Schafers, W. Haverkamp, and G Breithardt, Molecular mechanisms of inherited ventricular arrhythmias. Herz,2002.27(8):712-39.
[2]Viswanathan, P.C. and J.R. Balser, Inherited sodium channelopathies:a continuum of channel dysfunction. Trends Cardiovasc Med,2004.14(1): 28-35.
[3]Veldkamp, M.W., P.C. Viswanathan, C. Bezzina, A. Baartscheer, A.A. Wilde, and J.R. Balser, Two distinct congenital arrhythmias evoked by a multidysfunctional Na(+) channel. Circ Res,2000.86(9):E91-7.
[4]Wan, X., S. Chen, A. Sadeghpour, Q. Wang, and G.E. Kirsch, Accelerated inactivation in a mutant Na(+) channel associated with idiopathic ventricular fibrillation. Am J Physiol Heart Circ Physiol,2001.280(1):H354-60.
[5]Wang, D.W., P.C. Viswanathan, J.R. Balser, A.L. George, Jr., and D.W. Benson, Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation, 2002.105(3):341-6.
[6]Makielski, J.C. and A.L. Farley, Na(+) current in human ventricle: implications for sodium loading and homeostasis. J Cardiovasc Electrophysiol,2006.17 Suppl 1:S15-S20.
[7]Balser, J.R., Sodium "channelopathies" and sudden death:must you be so sensitive? Circ Res,1999.85(9):872-4.
[8]Matsuda, J.J., H. Lee, and E.F. Shibata, Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation. Circ Res,1992.70(1): 199-207.
[9]Matsuda, J.J., H.C. Lee, and E.F. Shibata, Acetylcholine reversal of isoproterenol-stimulated sodium currents in rabbit ventricular myocytes. Circ Res,1993.72(3):517-25.
[10]Sen, L., Y. Sakaguchi, and G. Cui, G protein modulates thyroid hormone-induced Na(+) channel activation in ventricular myocytes. Am J Physiol Heart Circ Physiol,2002.283(5):H2119-29.
[11]Shang, L.L., S. Sanyal, A.E. Pfahnl, Z. Jiao, J. Allen, H. Liu, and S.C. Dudley, Jr., NF-kappaB-dependent transcriptional regulation of the cardiac scn5a sodium channel by angiotensin Ⅱ. Am J Physiol Cell Physiol,2008.294(1): C372-9.
[12]Goldin, A.L., Resurgence of sodium channel research. Annu Rev Physiol, 2001.63:871-94.
[13]Haufe, V., J.A. Camacho, R. Dumaine, B. Gunther, C. Bollensdorff, G.S. von Banchet, K. Benndorf, and T. Zimmer, Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. J Physiol,2005.564(Pt 3):683-96.
[14]Kaufmann, S.G., R.E. Westenbroek, C. Zechner, A.H. Maass, S. Bischoff, J. Muck, E. Wischmeyer, T. Scheuer, and S.K. Maier, Functional protein expression of multiple sodium channel alpha- and beta-subunit isoforms in neonatal cardiomyocytes. J Mol Cell Cardiol,2009.48(1):261-9.
[15]Brette, F. and C.H. Orchard, No apparent requirement for neuronal sodium channels in excitation-contraction coupling in rat ventricular myocytes. Circ Res,2006.98(5):667-74.
[16]Maier, S.K., R.E. Westenbroek, K.A. McCormick, R. Curtis, T. Scheuer, and W.A. Catterall, Distinct subcellular localization of different sodium channel alpha and beta subunits in single ventricular myocytes from mouse heart. Circulation,2004.109(11):1421-7.
[17]Maier, S.K., R.E. Westenbroek, K.A. Schenkman, E.O. Feigl, T. Scheuer, and W.A. Catterall, An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart. Proc Natl Acad Sci U S A,2002.99(6):4073-8.
[18]Dhar Malhotra, J., C. Chen, I. Rivolta, H. Abriel, R. Malhotra, L.N. Mattei, F.C. Brosius, R.S. Kass, and L.L. Isom, Characterization of sodium channel alpha- and beta-subunits in rat and mouse cardiac myocytes. Circulation, 2001.103(9):1303-10.
[19]Fahmi, A.I., M. Patel, E.B. Stevens, A.L. Fowden, J.E. John,3rd, K. Lee, R. Pinnock, K. Morgan, A.P. Jackson, and J.I. Vandenberg, The sodium channel beta-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart. J Physiol,2001.537(Pt 3):693-700.
[20]Johnson, D. and E.S. Bennett, Isoform-specific effects of the beta2 subunit on voltage-gated sodium channel gating. J Biol Chem,2006.281(36): 25875-81.
[21]Ko, S.H., P.W. Lenkowski, H.C. Lee, J.P. Mounsey, and M.K. Patel, Modulation of Na(v)1.5 by betal-- and beta3-subunit co-expression in mammalian cells. Pflugers Arch,2005.449(4):403-12.
[22]Zimmer, T. and K. Benndorf, The intracellular domain of the beta 2 subunit modulates the gating of cardiac Na v 1.5 channels. Biophys J,2007.92(11): 3885-92.
[23]Liang, H.M., M. Tang, C.J. Liu, H.Y. Luo, Y.L. Song, X.W. Hu, J.Y. Xi, L.L. Gao, B. Nie, S.Y. Li, L.L. Lai, and J. Hescheler, Muscarinic cholinergic regulation of L-type calcium channel in heart of embryonic mice at different developmental stages. Acta Pharmacol Sin,2004.25(11):1450-7.
[24]Song, GL., M. Tang, C.J. Liu, H.Y. Luo, H.M. Liang, X.W. Hu, J.Y. Xi, L.L. Gao, B. Fleischmann, and J. Hescheler, Developmental changes in functional expression and beta-adrenergic regulation of I(f) in the heart of mouse embryo. Cell Res,2002.12(5-6):385-94.
[25]Davies, M.P., R.H. An, P. Doevendans, S. Kubalak, K.R. Chien, and R.S. Kass, Developmental changes in ionic channel activity in the embryonic murine heart. Circ Res,1996.78(1):15-25.
[26]Liu, W., K. Yasui, A. Arai, K. Kamiya, J. Cheng, I. Kodama, and J. Toyama, beta-adrenergic modulation of L-type Ca2+ channel currents in early-stage embryonic mouse heart. Am J Physiol,1999.276(2 Pt 2):H608-13.
[27]Yasui, K., W. Liu, T. Opthof, K. Kada, J.K. Lee, K. Kamiya, and I. Kodama, I(f) current and spontaneous activity in mouse embryonic ventricular myocytes. Circ Res,2001.88(5):536-42.
[28]Attwell, D., I. Cohen, D. Eisner, M. Ohba, and C. Ojeda, The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres. Pflugers Arch,1979.379(2):137-42.
[29]Baruscotti, M., D. DiFrancesco, and R.B. Robinson, A TTX-sensitive inward sodium current contributes to spontaneous activity in newborn rabbit sino-atrial node cells. J Physiol,1996.492 (Pt 1):21-30.
[30]Saint, D.A., The cardiac persistent sodium current:an appealing therapeutic target? Br J Pharmacol,2008.153(6):1133-42.
[31]Yokoshiki, H. and N. Tohse, Developmental Changes of Ion Channels., in Heart Physiology and Pathophysiology (Fourth Edition), N. Sperelakis, Y. Kurachi, A. Terzic, and M.V. Cohen, Editors.2001, Academic Press:New York. p.719-735.
[32]Bohle, T. and K. Benndorf, Voltage-dependent properties of three different gating modes in single cardiac Na+ channels. Biophys J,1995.69(3): 873-82.
[33]Bohle, T., M. Steinbis, C. Biskup, R. Koopmann, and K. Benndorf, Inactivation of single cardiac Na+ channels in three different gating modes. Biophys J,1998.75(4):1740-8.
[34]Nguyen, T.P., D.W. Wang, T.H. Rhodes, and A.L. George, Jr., Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia. Circ Res,2008.102(3):364-71.
[35]Lei, M., S.A. Jones, J. Liu, M.K. Lancaster, S.S. Fung, H. Dobrzynski, P. Camelliti, S.K. Maier, D. Noble, and M.R. Boyett, Requirement of neuronal-and cardiac-type sodium channels for murine sinoatrial node pacemaking. J Physiol,2004.559(Pt 3):835-48.
[36]Haufe, V, J.M. Cordeiro, T. Zimmer, Y.S. Wu, S. Schiccitano, K. Benndorf, and R. Dumaine, Contribution of neuronal sodium channels to the cardiac fast sodium current INa is greater in dog heart Purkinje fibers than in ventricles. Cardiovasc Res,2005.65(1):117-27.
[37]Dominguez, J.N., F. Navarro, D. Franco, R.P. Thompson, and A.E. Aranega, Temporal and spatial expression pattern of betal sodium channel subunit during heart development. Cardiovasc Res,2005.65(4):842-50.
[38]Baroudi, G., E. Carbonneau, V. Pouliot, and M. Chahine, SCN5A mutation (T1620M) causing Brugada syndrome exhibits different phenotypes when expressed in Xenopus oocytes and mammalian cells. FEBS Lett,2000. 467(1):12-6.
[39]Nuss, H.B., N. Chiamvimonvat, M.T. Perez-Garcia, G.F. Tomaselli, and E. Marban, Functional association of the beta 1 subunit with human cardiac (hH1) and rat skeletal muscle (mu 1) sodium channel alpha subunits expressed in Xenopus oocytes. J Gen Physiol,1995.106(6):1171-91.
[1]Wichter, T., E. Schulze-Bahr, L. Eckardt, M. Paul, B. Levkau, M. Meyborg, M. Schafers, W. Haverkamp, and G Breithardt, Molecular mechanisms of inherited ventricular arrhythmias. Herz,2002.27(8):712-39.
[2]Viswanathan, P.C. and J.R. Balser, Inherited sodium channelopathies:a continuum of channel dysfunction. Trends Cardiovasc Med,2004.14(1): 28-35.
[3]Veldkamp, M.W., P.C. Viswanathan, C. Bezzina, A. Baartscheer, A.A. Wilde, and J.R. Balser, Two distinct congenital arrhythmias evoked by a multidysfunctional Na(+) channel. Circ Res,2000.86(9):E91-7.
[4]Wan, X., S. Chen, A. Sadeghpour, Q. Wang, and GE. Kirsch, Accelerated inactivation in a mutant Na(+) channel associated with idiopathic ventricular fibrillation. Am J Physiol Heart Circ Physiol,2001.280(1):H354-60.
[5]Wang, D.W., P.C. Viswanathan, J.R. Balser, A.L. George, Jr., and D.W. Benson, Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation, 2002.105(3):341-6.
[6]Makielski, J.C. and A.L. Farley, Na(+) current in human ventricle: implications for sodium loading and homeostasis. J Cardiovasc Electrophysiol,2006.17 Suppl 1:S15-S20.
[7]Balser, J.R., Sodium "channelopathies" and sudden death:must you be so sensitive? Circ Res,1999.85(9):872-4.
[8]Matsuda, J.J., H. Lee, and E.F. Shibata, Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation. Circ Res,1992.70(1): 199-207.
[9]Matsuda, J.J., H.C. Lee, and E.F. Shibata, Acetylcholine reversal of isoproterenol-stimulated sodium currents in rabbit ventricular myocytes. Circ Res,1993.72(3):517-25.
[10]Sen, L., Y. Sakaguchi, and G. Cui, G protein modulates thyroid hormone-induced Na(+) channel activation in ventricular myocytes. Am J Physiol Heart Circ Physiol,2002.283(5):H2119-29.
[11]Shang, L.L., S. Sanyal, A.E. Pfahnl, Z. Jiao, J. Allen, H. Liu, and S.C. Dudley, Jr., NF-kappaB-dependent transcriptional regulation of the cardiac scn5a sodium channel by angiotensin Ⅱ. Am J Physiol Cell Physiol,2008.294(1): C372-9.
[12]Goldin, A.L., Resurgence of sodium channel research. Annu Rev Physiol, 2001.63:871-94.
[13]Haufe, V., J.A. Camacho, R. Dumaine, B. Gunther, C. Bollensdorff, G.S. von Banchet, K. Benndorf, and T. Zimmer, Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. J Physiol,2005.564(Pt 3):683-96.
[14]Kaufmann, S.G., R.E. Westenbroek, C. Zechner, A.H. Maass, S. Bischoff, J. Muck, E. Wischmeyer, T. Scheuer, and S.K. Maier, Functional protein expression of multiple sodium channel alpha- and beta-subunit isoforms in neonatal cardiomyocytes. J Mol Cell Cardiol,2009.48(1):261-9.
[15]Brette, F. and C.H. Orchard, No apparent requirement for neuronal sodium channels in excitation-contraction coupling in rat ventricular myocytes. Circ Res,2006.98(5):667-74.
[16]Maier, S.K., R.E. Westenbroek, K.A. McCormick, R. Curtis, T. Scheuer, and W.A. Catterall, Distinct subcellular localization of different sodium channel alpha and beta subunits in single ventricular myocytes from mouse heart. Circulation,2004.109(11):1421-7.
[17]Maier, S.K., R.E. Westenbroek, K.A. Schenkman, E.O. Feigl, T. Scheuer, and W.A. Catterall, An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart. Proc Natl Acad Sci U S A,2002.99(6):4073-8.
[18]Dhar Malhotra, J., C. Chen, I. Rivolta, H. Abriel, R. Malhotra, L.N. Mattei, F.C. Brosius, R.S. Kass, and L.L. Isom, Characterization of sodium channel alpha-and beta-subunits in rat and mouse cardiac myocytes. Circulation, 2001.103(9):1303-10.
[19]Fahmi, A.I., M. Patel, E.B. Stevens, A.L. Fowden, J.E. John,3rd, K. Lee, R. Pinnock, K. Morgan, A.P. Jackson, and J.I. Vandenberg, The sodium channel beta-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart. J Physiol,2001.537(Pt 3):693-700.
[20]Johnson, D. and E.S. Bennett, Isoform-specific effects of the beta2 subunit on voltage-gated sodium channel gating. J Biol Chem,2006.281(36): 25875-81.
[21]Ko, S.H., P.W. Lenkowski, H.C. Lee, J.P. Mounsey, and M.K. Patel, Modulation of Na(v)1.5 by betal-- and beta3-subunit co-expression in mammalian cells. Pflugers Arch,2005.449(4):403-12.
[22]Zimmer, T. and K. Benndorf, The intracellular domain of the beta 2 subunit modulates the gating of cardiac Na v 1.5 channels. Biophys J,2007.92(11): 3885-92.
[23]Liang, H.M., M. Tang, C.J. Liu, H.Y. Luo, Y.L. Song, X.W. Hu, J.Y. Xi, L.L. Gao, B. Nie, S.Y. Li, L.L. Lai, and J. Hescheler, Muscarinic cholinergic regulation of L-type calcium channel in heart of embryonic mice at different developmental stages. Acta Pharmacol Sin,2004.25(11):1450-7.
[24]Song, G.L., M. Tang, C.J. Liu, H.Y. Luo, H.M. Liang, X.W. Hu, J.Y. Xi, L.L. Gao, B. Fleischmann, and J. Hescheler, Developmental changes in functional expression and beta-adrenergic regulation of I(f) in the heart of mouse embryo. Cell Res,2002.12(5-6):385-94.
[25]Davies, M.P., R.H. An, P. Doevendans, S. Kubalak, K.R. Chien, and R.S. Kass, Developmental changes in ionic channel activity in the embryonic murine heart. Circ Res,1996.78(1):15-25.
[26]Liu, W., K. Yasui, A. Arai, K. Kamiya, J. Cheng, I. Kodama, and J. Toyama, beta-adrenergic modulation of L-type Ca2+-channel currents in early-stage embryonic mouse heart. Am J Physiol,1999.276(2 Pt 2):H608-13.
[27]Yasui, K., W. Liu, T. Opthof, K. Kada, J.K. Lee, K. Kamiya, and I. Kodama, I(f) current and spontaneous activity in mouse embryonic ventricular myocytes. Circ Res,2001.88(5):536-42.
[28]Attwell, D., I. Cohen, D. Eisner, M. Ohba, and C. Ojeda, The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres. Pflugers Arch,1979.379(2):137-42.
[29]Baruscotti, M., D. DiFrancesco, and R.B. Robinson, A TTX-sensitive inward sodium current contributes to spontaneous activity in newborn rabbit sino-atrial node cells. J Physiol,1996.492 (Pt 1):21-30.
[30]Saint, D.A., The cardiac persistent sodium current:an appealing therapeutic-target? Br J Pharmacol,2008.153(6):1133-42.
[31]Yokoshiki, H. and N. Tohse, Developmental Changes of Ion Channels., in Heart Physiology and Pathophysiology (Fourth Edition), N. Sperelakis, Y. Kurachi, A. Terzic, and M.V. Cohen, Editors.2001, Academic Press:New York. p.719-735.
[32]Bohle, T. and K. Benndorf, Voltage-dependent properties of three different gating modes in single cardiac Na+ channels. Biophys J,1995.69(3): 873-82.
[33]Bohle, T., M. Steinbis, C. Biskup, R. Koopmann, and K. Benndorf, Inactivation of single cardiac Na+ channels in three different gating modes. Biophys J,1998.75(4):1740-8.
[34]Nguyen, T.P., D.W. Wang, T.H. Rhodes, and A.L. George, Jr., Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia. Circ Res,2008.102(3):364-71.
[35]Lei, M., S.A. Jones, J. Liu, M.K. Lancaster, S.S. Fung, H. Dobrzynski, P. Camelliti, S.K. Maier, D. Noble, and M.R. Boyett, Requirement of neuronal-and cardiac-type sodium channels for murine sinoatrial node pacemaking. J Physiol,2004.559(Pt 3):835-48.
[36]Haufe, V., J.M. Cordeiro, T. Zimmer, Y.S. Wu, S. Schiccitano, K. Benndorf, and R. Dumaine, Contribution of neuronal sodium channels to the cardiac fast sodium current INa is greater in dog heart Purkinje fibers than in ventricles. Cardiovasc Res,2005.65(1):117-27.
[37]Dominguez, J.N., F. Navarro, D. Franco, R.P. Thompson, and A.E. Aranega, Temporal and spatial expression pattern of betal sodium channel subunit during heart development. Cardiovasc Res,2005.65(4):842-50.
[38]Baroudi, G, E. Carbonneau, V. Pouliot, and M. Chahine, SCN5A mutation (T1620M) causing Brugada syndrome exhibits different phenotypes when expressed in Xenopus oocytes and mammalian cells. FEBS Lett,2000. 467(1):12-6.
[39]Nuss, H.B., N. Chiamvimonvat, M.T. Perez-Garcia, G.F. Tomaselli, and E. Marban, Functional association of the beta 1 subunit with human cardiac (hH1) and rat skeletal muscle (mu 1) sodium channel alpha subunits expressed in Xenopus oocytes. J Gen Physiol,1995.106(6):1171-91.
[1]Catterall, W.A., From ionic currents to molecular mechanisms:the structure and function of voltage-gated sodium channels. Neuron,2000.26(1):13-25.
[2]Goldin, A.L., R.L. Barchi, J.H. Caldwell, F. Hofmann, J.R. Howe, J.C. Hunter, R.G Kallen, G. Mandel, M.H. Meisler, Y.B. Netter, M. Noda, M.M. Tamkun, S.G. Waxman, J.N. Wood, and W.A. Catterall, Nomenclature of voltage-gated sodium channels. Neuron,2000.28(2):365-8.
[3]Kaufmann, S.G, R.E. Westenbroek, C. Zechner, A.H. Maass, S. Bischoff, J. Muck, E. Wischmeyer, T. Scheuer, and S.K. Maier, Functional protein expression of multiple sodium channel alpha-and beta-subunit isoforms in neonatal cardiomyocytes. J Mol Cell Cardiol,2010.48(1):261-9.
[4]Haufe, V., J.A. Camacho, R. Dumaine, B. Gunther, C. Bollensdorff, G.S. von Banchet, K. Benndorf, and T. Zimmer, Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. J Physiol,2005.564(Pt 3):683-96.
[5]Makielski, J.C., B. Ye, C.R. Valdivia, M.D. Pagel, J. Pu, D.J. Tester, and M.J. Ackerman, A ubiquitous splice variant and a common polymorphism affect heterologous expression of recombinant human SCN5A heart sodium channels. Circ Res,2003.93(9):821-8.
[6]Abriel, H. and R.S. Kass, Regulation of the voltage-gated cardiac sodium channel Nav1.5 by interacting proteins. Trends Cardiovasc Med,2005.15(1): 35-40.
[7]Hu, D., H. Barajas-Martinez, E. Burashnikov, M. Springer, Y. Wu, A. Varro, R. Pfeiffer, T.T. Koopmann, J.M. Cordeiro, A. Guerchicoff, G.D. Pollevick, and C. Antzelevitch, A mutation in the beta 3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype. Circ Cardiovasc Genet,2009.2(3): 270-8.
[8]Ko, S.H., P.W. Lenkowski, H.C. Lee, J.P. Mounsey, and M.K. Patel, Modulation of Na(v)1.5 by betal-- and beta3-subunit co-expression in mammalian cells. Pflugers Arch,2005.449(4):403-12.
[9]Medeiros-Domingo, A., T. Kaku, D.J. Tester, P. Iturralde-Torres, A. Itty, B. Ye, C. Valdivia, K. Ueda, S. Canizales-Quinteros, M.T. Tusie-Luna, J.C. Makielski, and M.J. Ackerman, SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome. Circulation,2007.116(2):134-42.
[10]Watanabe, H., T.T. Koopmann, S. Le Scouarnec, T. Yang, C.R. Ingram, J.J. Schott, S. Demolombe, V. Probst, F. Anselme, D. Escande, A.C. Wiesfeld, A. Pfeufer, S. Kaab, H.E. Wichmann, C. Hasdemir, Y. Aizawa, A.A. Wilde, D.M. Roden, and C.R. Bezzina, Sodium channel betal subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest,2008.118(6):2260-8.
[11]Dhar Malhotra, J., C. Chen, I. Rivolta, H. Abriel, R. Malhotra, L.N. Mattei, F.C. Brosius, R.S. Kass, and L.L. Isom, Characterization of sodium channel alpha-and beta-subunits in rat and mouse cardiac myocytes. Circulation,2001. 103(9):1303-10.
[12]Yu, F.H., R.E. Westenbroek, I. Silos-Santiago, K.A. McCormick, D. Lawson, P. Ge, H. Ferriera, J. Lilly, P.S. DiStefano, W.A. Catterall, T. Scheuer, and R, Curtis, Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2. J Neurosci,2003.23(20):7577-85.
[13]Isom, L.L., D.S. Ragsdale, K.S. De Jongh, R.E. Westenbroek, B.F. Reber, T. Scheuer, and W.A. Catterall, Structure and function of the beta 2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell, 1995.83(3):433-42.
[14]Johnson, D. and E.S. Bennett, Isoform-specific effects of the beta2 subunit on voltage-gated sodium channel gating. J Biol Chem,2006.281(36):25875-81.
[15]Zimmer, T. and K. Benndorf, The intracellular domain of the beta 2 subunit modulates the gating of cardiac Na v 1.5 channels. Biophys J,2007.92(11): 3885-92.
[16]Fahmi, A.I., M. Patel, E.B. Stevens, A.L. Fowden, J.E. John,3rd, K. Lee, R. Pinnock, K. Morgan, A.P. Jackson, and J.I. Vandenberg, The sodium channel beta-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart. J Physiol,2001.537(Pt 3):693-700.
[17]Malhotra, J.D., K. Kazen-Gillespie, M. Hortsch, and L.L. Isom, Sodium channel beta subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact. J Biol Chem,2000.275(15):11383-8.
[18]Srinivasan, J., M. Schachner, and W.A. Catterall, Interaction of voltage-gated sodium channels with the extracellular matrix molecules tenascin-C and tenascin-R. Proc Natl Acad Sci U S A,1998.95(26):15753-7.
[19]Chioni, A.M., W.J. Brackenbury, J.D. Calhoun, L.L. Isom, and M.B. Djamgoz, A novel adhesion molecule in human breast cancer cells:voltage-gated Na+ channel betal subunit. Int J Biochem Cell Biol,2009.41(5):1216-27.
[20]Malhotra, J.D., M.C. Koopmann, K.A. Kazen-Gillespie, N. Fettman, M. Hortsch, and L.L. Isom, Structural requirements for interaction of sodium channel beta 1 subunits with ankyrin. J Biol Chem,2002.277(29):26681-8.
[21]Malhotra, J.D., V. Thyagarajan, C. Chen, and L.L. Isom, Tyrosine-phosphorylated and nonphosphorylated sodium channel beta1 subunits are differentially localized in cardiac myocytes. J Biol Chem,2004. 279(39):40748-54.
[22]Cohen, S.A., Immunocytochemical localization of rH1 sodium channel in adult rat heart atria and ventricle. Presence in terminal intercalated disks. Circulation,1996.94(12):3083-6.
[23]Maier, S.K., R.E. Westenbroek, K.A. McCormick, R. Curtis, T. Scheuer, and W.A. Catterall, Distinct subcellular localization of different sodium channel alpha and beta subunits in single ventricular myocytes from mouse heart. Circulation,2004.109(11):1421-7.
[24]Brette, F. and C.H. Orchard, Density and sub-cellular distribution of cardiac and neuronal sodium channel isoforms in rat ventricular myocytes. Biochem Biophys Res Commun,2006.348(3):1163-6.
[25]Baba, S., W. Dun, C. Cabo, and P.A. Boyden, Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia. Circulation,2005.112(16):2386-96.
[26]Mohler, P.J., I. Splawski, C. Napolitano, G. Bottelli, L. Sharpe, K. Timothy, S.G. Priori, M.T. Keating, and V. Bennett, A cardiac arrhythmia syndrome caused by loss of ankyrin-B function. Proc Natl Acad Sci U S A,2004. 101(24):9137-42.
[27]Zimmer, T., C. Biskup, S. Dugarmaa, F. Vogel, M. Steinbis, T. Bohle, Y.S. Wu, R. Dumaine, and K. Benndorf, Functional expression of GFP-linked human heart sodium channel (hH1) and subcellular localization of the a subunit in HEK293 cells and dog cardiac myocytes. J Membr Biol,2002.186(1):1-12.
[28]Tateyama, M., H. Liu, A.S. Yang, J.W. Cormier, and R.S. Kass, Structural effects of an LQT-3 mutation on heart Na+ channel gating. Biophys J,2004. 86(3):1843-51.
[29]Coraboeuf, E., E. Deroubaix, and A. Coulombe, Effect of tetrodotoxin on action potentials of the conducting system in the dog heart. Am J Physiol, 1979.236(4):H561-7.
[30]Hodgkin, A.L. and A.F. Huxley, A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol, 1952.117(4):500-44.
[31]Armstrong, C.M., Sodium channels and gating currents. Physiol Rev,1981. 61(3):644-83.
[32]Stuhmer, W., F. Conti, H. Suzuki, X.D. Wang, M. Noda, N. Yahagi, H. Kubo, and S. Numa, Structural parts involved in activation and inactivation of the sodium channel. Nature,1989.339(6226):597-603.
[33]Yang, N. and R. Horn, Evidence for voltage-dependent S4 movement in sodium channels. Neuron,1995.15(1):213-8.
[34]Armstrong, C.M., F. Bezanilla, and E. Rojas, Destruction of sodium conductance inactivation in squid axons perfused with pronase. J Gen Physiol., 1973.62(4):375-91.
[35]Armstrong, C.M. and F. Bezanilla, Inactivation of the sodium channel. II. Gating current experiments. J Gen Physiol,1977.70(5):567-90.
[36]Vassilev, P.M., T. Scheuer, and W.A. Catterall, Identification of an intracellular peptide segment involved in sodium channel inactivation. Science,1988. 241(4873):1658-61.
[37]Patton, D.E., J.W. West, W.A. Catterall, and A.L. Goldin, Amino acid residues required for fast Na(+)-channel inactivation:charge neutralizations and deletions in the III-IV linker. Proc Natl Acad Sci U S A,1992.89(22): 10905-9.
[38]West, J.W., D.E. Patton, T. Scheuer, Y. Wang, A.L. Goldin, and W.A. Catterall, A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation. Proc Natl Acad Sci U S A,1992.89(22):10910-4.
[39]Kellenberger, S., T. Scheuer, and W.A. Catterall, Movement of the Na+ channel inactivation gate during inactivation. J Biol Chem,1996.271(48): 30971-9.
[40]Matsuda, J.J., H. Lee, and E.F. Shibata, Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation. Circ Res,1992.70(1):199-207.
[41]Matsuda, J.J., H.C. Lee, and E.F. Shibata, Acetylcholine reversal of isoproterenol-stimulated sodium currents in rabbit ventricular myocytes. Circ Res,1993.72(3):517-25.
[42]Shang, L.L., S. Sanyal, A.E. Pfahnl, Z. Jiao, J. Allen, H. Liu, and S.C. Dudley, Jr., NF-kappaB-dependent transcriptional regulation of the cardiac scn5a sodium channel by angiotensin Ⅱ. Am J Physiol Cell Physiol,2008.294(1): C372-9.
[43]Boixel, C., B. Gavillet, J.S. Rougier, and H. Abriel, Aldosterone increases voltage-gated sodium current in ventricular myocytes. Am J Physiol Heart Circ Physiol,2006.290(6):H2257-66.
[44]Sen, L., Y. Sakaguchi, and G. Cui, G protein modulates thyroid hormone-induced Na(+) channel activation in ventricular myocytes. Am J Physiol Heart Circ Physiol,2002.283(5):H2119-29.
[45]Ahmmed, G.U., Y. Xu, P. Hong Dong, Z. Zhang, J. Eiserich, and N. Chiamvimonvat, Nitric oxide modulates cardiac Na(+) channel via protein kinase A and protein kinase G. Circ Res,2001.89(11):1005-13.
[46]Bers, D.M., Cardiac excitation-contraction coupling. Nature,2002.415(6868): 198-205.
[47]Ono, K., T. Kiyosue, and M. Arita, Isoproterenol, DBcAMP, and forskolin inhibit cardiac sodium current. Am J Physiol,1989.256(6 Pt 1):C1131-7.
[48]Schubert, B., A.M. VanDongen, G.E. Kirsch, and A.M. Brown, Beta-adrenergic inhibition of cardiac sodium channels by dual G-protein pathways. Science,1989.245(4917):516-9.
[49]Lu, T., H.C. Lee, J.A. Kabat, and E.F. Shibata, Modulation of rat cardiac sodium channel by the stimulatory G protein alpha subunit. J Physiol,1999. 518 (Pt 2):371-84.
[50]Baba, S., W. Dun, and P.A. Boyden, Can PKA activators rescue Na+ channel function in epicardial border zone cells that survive in the infarcted canine heart? Cardiovasc Res,2004.64(2):260-7.
[51]Zhou, J., J. Yi, N. Hu, A.L. George, Jr., and K.T. Murray, Activation of protein kinase A modulates trafficking of the human cardiac sodium channel in Xenopus oocytes. Circ Res,2000.87(1):33-8.
[52]Wagner, S., N. Dybkova, E.C. Rasenack, C. Jacobshagen, L. Fabritz, P. Kirchhof, S.K. Maier, T. Zhang, G. Hasenfuss, J.H. Brown, D.M. Bers, and L.S. Maier, Ca2+/calmodulin-dependent protein kinase Ⅱ regulates cardiac Na+ channels. J Clin Invest,2006.116(12):3127-38.
[53]Soderling, T.R., B. Chang, and D. Brickey, Cellular signaling through multifunctional Ca2+/calmodulin-dependent protein kinase Ⅱ. J Biol Chem, 2001.276(6):3719-22.
[54]Maier, L.S. and D.M. Bers, Calcium, calmodulin, and calcium-calmodulin kinase Ⅱ:heartbeat to heartbeat and beyond. J Mol Cell Cardiol,2002.34(8): 919-39.
[55]Davis, M.J., X. Wu, T.R. Nurkiewicz, J. Kawasaki, P. Gui, M.A. Hill, and E. Wilson, Regulation of ion channels by protein tyrosine phosphorylation. Am J Physiol Heart Circ Physiol,2001.281(5):H1835-62.
[56]Ahern, C.A., J.F. Zhang, M.J. Wookalis, and R. Horn, Modulation of the cardiac sodium channel NaV1.5 by Fyn, a Src family tyrosine kinase. Circ Res, 2005.96(9):991-8.
[57]Liu, H., H.Y. Sun, C.P. Lau, and G.R. Li, Regulation of voltage-gated cardiac sodium current by epidermal growth factor receptor kinase in guinea pig ventricular myocytes. J Mol Cell Cardiol,2007.42(4):760-8.
[58]Arad, M., C.E. Seidman, and J.G Seidman, AMP-activated protein kinase in the heart:role during health and disease. Circ Res,2007.100(4):474-88.
[59]Gollob, M.H., Glycogen storage disease as a unifying mechanism of disease in the PRKAG2 cardiac syndrome. Biochem Soc Trans,2003.31(Pt 1):228-31.
[60]Light, P.E., C.H. Wallace, and J.R. Dyck, Constitutively active adenosine monophosphate-activated protein kinase regulates voltage-gated sodium channels in ventricular myocytes. Circulation,2003.107(15):1962-5.
[61]Molkentin, J.D., Calcineurin-NFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs. Cardiovasc Res,2004. 63(3):467-75.
[62]Dong, D., Y. Duan, J. Guo, D.E. Roach, S.L. Swirp, L. Wang, J.P. Lees-Miller, R.S. Sheldon, J.D. Molkentin, and H.J. Duff, Overexpression of calcineurin in mouse causes sudden cardiac death associated with decreased density of K+ channels. Cardiovasc Res,2003.57(2):320-32.
[63]Guo, J., S. Zhan, J. Somers, R.E. Westenbroek, W.A. Catterall, D.E. Roach, R.S. Sheldon, J.P. Lees-Miller, P. Li, Y. Shimoni, and H.J. Duff, Decrease in density of INa is in the common final pathway to heart block in murine hearts overexpressing calcineurin. Am J Physiol Heart Circ Physiol,2006.291(6): H2669-79.
[64]Murray, K.T., N.N. Hu, J.R. Daw, H.G. Shin, M.T. Watson, A.B. Mashbum, and A.L. George, Jr., Functional effects of protein kinase C activation on the human cardiac Na+ channel. Circ Res,1997.80(3):370-6.
[65]Bennett, V. and A.J. Baines, Spectrin and ankyrin-based pathways:metazoan inventions for integrating cells into tissues. Physiol Rev,2001.81(3):1353-92.
[66]Lemaillet, G, B. Walker, and S. Lambert, Identification of a conserved ankyrin-binding motif in the family of sodium channel alpha subunits. J Biol Chem,2003.278(30):27333-9.
[67]Priori, S.G, C. Napolitano, M. Gasparini, C. Pappone, P. Della Bella, M. Brignole, U. Giordano, T. Giovannini, C. Menozzi, R. Bloise, L. Crotti, L. Terreni, and P.J. Schwartz, Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome:A prospective evaluation of 52 families. Circulation,2000.102(20):2509-15.
[68]Mohler, P.J., I. Rivolta, C. Napolitano, G. LeMaillet, S. Lambert, S.G. Priori, and V. Bennett, Navl.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Navl.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A,2004.101(50):17533-8.
[69]Mohler, P.J., J.J. Schott, A.O. Gramolini, K.W. Dilly, S. Guatimosim, W.H. duBell, L.S. Song, K. Haurogne, F. Kyndt, M.E. Ali, T.B. Rogers, W.J. Lederer, D. Escande, H. Le Marec, and V. Bennett, Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature,2003. 421(6923):634-9.
[70]Chauhan, V.S., S. Tuvia, M. Buhusi, V. Bennett, and A.O. Grant, Abnormal cardiac Na(+) channel properties and QT heart rate adaptation in neonatal ankyrin(B) knockout mice. Circ Res,2000.86(4):441-7.
[71]Baroudi, G, E. Carbonneau, V. Pouliot, and M. Chahine, SCN5A mutation (T1620M) causing Brugada syndrome exhibits different phenotypes when expressed in Xenopus oocytes and mammalian cells. FEBS Lett,2000.467(1): 12-6.
[72]Nuss, H.B., N. Chiamvimonvat, M.T. Perez-Garcia, GF. Tomaselli, and E. Marban, Functional association of the beta 1 subunit with human cardiac (hH1) and rat skeletal muscle (mu 1) sodium channel alpha subunits expressed in Xenopus oocytes. J Gen Physiol,1995.106(6):1171-91.
[73]Saimi, Y. and C. Kung, Calmodulin as an ion channel subunit. Annu Rev Physiol,2002.64:289-311.
[74]Herzog, R.I., C. Liu, S.G. Waxman, and T.R. Cummins, Calmodulin binds to the C terminus of sodium channels Nav1.4 and Navl.6 and differentially modulates their functional properties. J Neurosci,2003.23(23):8261-70.
[75]Deschenes, I., N. Neyroud, D. DiSilvestre, E. Marban, D.T. Yue, and GF. Tomaselli, Isoform-specific modulation of voltage-gated Na(+) channels by calmodulin. Circ Res,2002.90(4):E49-57.
[76]Kim, J., S. Ghosh, H. Liu, M. Tateyama, R.S. Kass, and GS. Pitt, Calmodulin mediates Ca2+ sensitivity of sodium channels. J Biol Chem,2004.279(43): 45004-12.
[77]Tan, H.L., S. Kupershmidt, R. Zhang, S. Stepanovic, D.M. Roden, A.A. Wilde, M.E. Anderson, and J.R. Balser, A calcium sensor in the sodium channel modulates cardiac excitability. Nature,2002.415(6870):442-7.
[78]Wingo, T.L., V.N. Shah, M.E. Anderson, T.P. Lybrand, W.J. Chazin, and J.R. Balser, An EF-hand in the sodium channel couples intracellular calcium to cardiac excitability. Nat Struct Mol Biol,2004.11(3):219-25.
[79]Motoike, H.K., H. Liu, I.W. Glaaser, A.S. Yang, M. Tateyama, and R.S. Kass, The Na+ channel inactivation gate is a molecular complex:a novel role of the COOH-terminal domain. J Gen Physiol,2004.123(2):155-65.
[80]Hicke, L. and R. Dunn, Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu Rev Cell Dev Biol,2003.19:141-72.
[81]Rotin, D., O. Staub, and R. Haguenauer-Tsapis, Ubiquitination and endocytosis of plasma membrane proteins:role of Nedd4/Rsp5p family of ubiquitin-protein ligases. J Membr Biol,2000.176(1):1-17.
[82]Staub, O. and D. Rotin, WW domains. Structure,1996.4(5):495-9.
[83]Fotia, A.B., J. Ekberg, D.J. Adams, D.I. Cook, P. Poronnik, and S. Kumar, Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2. J Biol Chem,2004.279(28):28930-5.
[84]Rougier, J.S., M.X. van Bemmelen, M.C. Bruce, T. Jespersen, B. Gavillet, F. Apotheloz, S. Cordonier, O. Staub, D. Rotin, and H. Abriel, Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins. Am J Physiol Cell Physiol,2005.288(3): C692-701.
[85]Abriel, H., E. Kamynina, J.D. Horisberger, and O. Staub, Regulation of the cardiac voltage-gated Na+ channel (H1) by the ubiquitin-protein ligase Nedd4. FEBS Lett,2000.466(2-3):377-80.
[86]van Bemmelen, M.X., J.S. Rougier, B. Gavillet, F. Apotheloz, D. Daidie, M. Tateyama, I. Rivolta, M.A. Thomas, R.S. Kass, O. Staub, and H. Abriel, Cardiac voltage-gated sodium channel Navl.5 is regulated by Nedd4-2 mediated ubiquitination. Circ Res,2004.95(3):284-91.
[87]Ingham, R.J., G. Gish, and T. Pawson, The Nedd4 family of E3 ubiquitin ligases:functional diversity within a common modular architecture. Oncogene, 2004.23(11):1972-84.
[88]Albrecht, D.E. and S.C. Froehner, Syntrophins and dystrobrevins:defining the dystrophin scaffold at synapses. Neurosignals,2002.11(3):123-9.
[89]Gee, S.H., R. Madhavan, S.R. Levinson, J.H. Caldwell, R. Sealock, and S.C. Froehner, Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins. J Neurosci,1998.18(1):128-37.
[90]Zhou, J., H.G Shin, J. Yi, W. Shen, C.P. Williams, and K.T. Murray, Phosphorylation and putative ER retention signals are required for protein kinase A-mediated potentiation of cardiac sodium current. Circ Res,2002. 91(6):540-6.
[91]Ou, Y., P. Strege, S.M. Miller, J. Makielski, M. Ackerman, S.J. Gibbons, and G Farrugia, Syntrophin gamma 2 regulates SCN5A gating by a PDZ domain-mediated interaction. J Biol Chem,2003.278(3):1915-23.
[92]Finsterer, J. and C. Stollberger, The heart in human dystrophinopathies. Cardiology,2003.99(1):1-19.
[93]Liu, C., S.D. Dib-Hajj, and S.G. Waxman, Fibroblast growth factor homologous factor 1B binds to the C terminus of the tetrodotoxin-resistant sodium channel rNav1.9a (NaN). J Biol Chem,2001.276(22):18925-33.
[94]Liu, C.J., S.D. Dib-Hajj, M. Renganathan, T.R. Cummins, and S.G. Waxman, Modulation of the cardiac sodium channel Navl.5 by fibroblast growth factor homologous factor 1B. J Biol Chem,2003.278(2):1029-36.
[95]Wehrens, X.H., H. Abriel, C. Cabo, J. Benhorin, and R.S. Kass, Arrhythmogenic mechanism of an LQT-3 mutation of the human heart Na(+) channel alpha-subunit:A computational analysis. Circulation,2000.102(5): 584-90.
[96]Brugada, P. and J. Brugada, Right bundle branch block, persistent ST segment elevation and sudden cardiac death:a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol,1992.20(6):1391-6.
[97]Miyazaki, T., H. Mitamura, S. Miyoshi, K. Soejima, Y. Aizawa, and S. Ogawa, Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. J Am Coll Cardiol,1996.27(5):1061-70.
[98]Wilde, A.A., C. Antzelevitch, M. Borggrefe, J. Brugada, R. Brugada, P. Brugada, D. Corrado, R.N. Hauer, R.S. Kass, K. Nademanee, S.G. Priori, and J.A. Towbin, Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation,2002.106(19):2514-9.
[99]Zimmer, T. and R. Surber, SCN5A channelopathies--an update on mutations and mechanisms. Prog Biophys Mol Biol,2008.98(2-3):120-36.
[100]Valdivia, C.R., D.J. Tester, B.A. Rok, C.B. Porter, T.M. Munger, A. Jahangir, J.C. Makielski, and M.J. Ackerman, A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs. Cardiovasc Res,2004. 62(1):53-62.
[101]Kyndt, F., V. Probst, F. Potet, S. Demolombe, J.C. Chevallier, I. Baro, J.P. Moisan, P. Boisseau, J.J. Schott, D. Escande, and H. Le Marec, Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family. Circulation,2001.104(25):3081-6.
[102]Amin, A.S., A.O. Verkerk, Z.A. Bhuiyan, A.A. Wilde, and H.L. Tan, Novel Brugada syndrome-causing mutation in ion-conducting pore of cardiac Na+ channel does not affect ion selectivity properties. Acta Physiol Scand,2005. 185(4):291-301.
[103]Bezzina, C., M.W. Veldkamp, M.P. van Den Berg, A.V. Postma, M.B. Rook, J.W. Viersma, I.M. van Langen, G. Tan-Sindhunata, M.T. Bink-Boelkens, A.H. van Der Hout, M.M. Mannens, and A.A. Wilde, A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res,1999. 85(12):1206-13.
[104]Dumaine, R., J.A. Towbin, P. Brugada, M. Vatta, D.V. Nesterenko, V.V. Nesterenko, J. Brugada, R. Brugada, and C. Antzelevitch, Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circ Res,1999.85(9):803-9.
[105]Smits, J.P., T.T. Koopmann, R. Wilders, M.W. Veldkamp, T. Opthof, Z.A. Bhuiyan, M.M. Mannens, J.R. Balser, H.L. Tan, C.R. Bezzina, and A.A. Wilde, A mutation in the human cardiac sodium channel (E161K) contributes to sick sinus syndrome, conduction disease and Brugada syndrome in two families. J Mol Cell Cardiol,2005.38(6):969-81.
[106]Smits, J.P., L. Eckardt, V. Probst, C.R. Bezzina, J.J. Schott, C.A. Remme, W. Haverkamp, G. Breithardt, D. Escande, E. Schulze-Bahr, H. LeMarec, and A.A. Wilde, Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. J Am Coll Cardiol,2002.40(2):350-6.
[107]Antzelevitch, C., Cellular basis for the repolarization waves of the ECG Ann N Y Acad Sci,2006.1080:268-81.
[108]Meregalli, P.G, A.A. Wilde, and H.L. Tan, Pathophysiological mechanisms of Brugada syndrome:depolarization disorder, repolarization disorder, or more? Cardiovasc Res,2005.67(3):367-78.
[109]Amin, A.S., P.G Meregalli, A. Bardai, A.A. Wilde, and H.L. Tan, Fever increases the risk for cardiac arrest in the Brugada syndrome. Ann Intern Med, 2008.149(3):216-8.
[110]Junttila, M.J., M. Gonzalez, E. Lizotte, B. Benito, K. Vernooy, A. Sarkozy, H.V. Huikuri, P. Brugada, J. Brugada, and R. Brugada, Induced Brugada-type electrocardiogram, a sign for imminent malignant arrhythmias. Circulation, 2008.117(14):1890-3.
[111]Matsuo, K., M. Akahoshi, S. Seto, and K. Yano, Disappearance of the Brugada-type electrocardiogram after surgical castration:a role for testosterone and an explanation for the male preponderance. Pacing Clin Electrophysiol,2003.26(7 Pt 1):1551-3.
[112]Shimizu, W., K. Matsuo, Y. Kokubo, K. Satomi, T. Kurita, T. Noda, N. Nagaya, K. Suyama, N. Aihara, S. Kamakura, N. Inamoto, M. Akahoshi, and H. Tomoike, Sex hormone and gender difference--role of testosterone on male predominance in Brugada syndrome. J Cardiovasc Electrophysiol,2007.18(4): 415-21.
[113]Postema, P.G, C. Wolpert, A.S. Amin, V. Probst, M. Borggrefe, D.M. Roden, S.G Priori, H.L. Tan, M. Hiraoka, J. Brugada, and A.A. Wilde, Drugs and Brugada syndrome patients:review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org). Heart Rhythm,2009.6(9): 1335-41.
[114]Brugada, J., P. Brugada, and R. Brugada, The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome. Europace,1999.1(3):156-66.
[115]Morita, H., J. Wu, and D.P. Zipes, The QT syndromes:long and short. Lancet, 2008.372(9640):750-63.
[116]Kapplinger, J.D., D.J. Tester, B.A. Salisbury, J.L. Carr, C. Harris-Kerr, G.D. Pollevick, A.A. Wilde, and M.J. Ackerman, Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm,2009.6(9): 1297-303.
[117]Wang, Q., J. Shen, I. Splawski, D. Atkinson, Z. Li, J.L. Robinson, A.J. Moss, J.A. Towbin, and M.T. Keating, SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell,1995.80(5):805-11.
[118]Bennett, P.B., K. Yazawa, N. Makita, and A.L. George, Jr., Molecular mechanism for an inherited cardiac arrhythmia. Nature,1995.376(6542): 683-5.
[119]Napolitano, C, S.G. Priori, P.J. Schwartz, R. Bloise, E. Ronchetti, J. Nastoli,G. Bottelli, M. Cerrone, and S. Leonardi, Genetic testing in the long QT syndrome:development and validation of an efficient approach to genotyping in clinical practice. JAMA,2005.294(23):2975-80.
[120]Tester, D.J., M.L. Will, C.M. Haglund, and M.J. Ackerman, Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm,2005.2(5):507-17.
[121]Potet, F., B. Chagot, M. Anghelescu, P.C. Viswanathan, S.Z. Stepanovic, S. Kupershmidt, W.J. Chazin, and J.R. Balser, Functional Interactions between Distinct Sodium Channel Cytoplasmic Domains through the Action of Calmodulin. J Biol Chem,2009.284(13):8846-54.
[122]Wang, D.W., K. Yazawa, A.L. George, Jr., and P.B. Bennett, Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome. Proc Natl Acad Sci U S A,1996.93(23):13200-5.
[123]Wedekind, H., J.P. Smits, E. Schulze-Bahr, R. Arnold, M.W. Veldkamp, T. Bajanowski, M. Borggrefe, B. Brinkmann, I. Warnecke, H. Funke, Z.A. Bhuiyan, A.A. Wilde, G. Breithardt, and W. Haverkamp, De novo mutation in the SCN5A gene associated with early onset of sudden infant death. Circulation,2001.104(10):1158-64.
[124]Ruan, Y., N. Liu, R. Bloise, C. Napolitano, and S.G. Priori, Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients. Circulation,2007.116(10):1137-44.
[125]Albert, C.M., E.G. Nam, E.B. Rimm, H.W. Jin, R.J. Hajjar, D.J. Hunter, C.A. MacRae, and P.T. Ellinor, Cardiac sodium channel gene variants and sudden cardiac death in women. Circulation,2008.117(1):16-23.
[126]Clancy, C.E., M. Tateyama, H. Liu, X.H. Wehrens, and R.S. Kass, Non-equilibrium gating in cardiac Na+ channels:an original mechanism of arrhythmia. Circulation,2003.107(17):2233-7.
[127]Rivolta, I., H. Abriel, M. Tateyama, H. Liu, M. Memmi, P. Vardas, C. Napolitano, S.G Priori, and R.S. Kass, Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes. J Biol Chem,2001.276(33): 30623-30.
[128]Dun, W. and P.A. Boyden, The Purkinje cell; 2008 style. J Mol Cell Cardiol, 2008.45(5):617-24.
[129]Haissaguerre, M., F. Extramiana, M. Hocini, B. Cauchemez, P. Jais, J.A. Cabrera, J. Farre, A. Leenhardt, P. Sanders, C. Scavee, L.F. Hsu, R. Weerasooriya, D.C. Shah, R. Frank, P. Maury, M. Delay, S. Garrigue, and J. Clementy, Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes. Circulation,2003.108(8):925-8.
[130]Yan, GX., Y. Wu, T. Liu, J. Wang, R.A. Marinchak, and P.R. Kowey, Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome:direct evidence from intracellular recordings in the intact left ventricular wall. Circulation,2001.103(23):2851-6.
[131]Benhorin, J., R. Taub, M. Goldmit, B. Kerem, R.S. Kass, I. Windman, and A. Medina, Effects of flecainide in patients with new SCN5A mutation: mutation-specific therapy for long-QT syndrome? Circulation,2000.101(14): 1698-706.
[132]Moss, A.J., W. Zareba, K.Q. Schwarz, S. Rosero, S. McNitt, and J.L. Robinson, Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. J Cardiovasc Electrophysiol,2008. 19(12):1289-93.
[133]Schwartz, P.J., S.G Priori, E.H. Locati, C. Napolitano, F. Cantu, J.A. Towbin, M.T. Keating, H. Hammoude, A.M. Brown, and L.S. Chen, Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+channel blockade and to increases in heart rate. Implications for gene-specific therapy. Circulation,1995.92(12):3381-6.
[134]Bankston, J.R. and R.S. Kass, Molecular determinants of local anesthetic action of beta-blocking drugs:Implications for therapeutic management of long QT syndrome variant 3. J Mol Cell Cardiol,2009.48(1):246-53.
[135]Fabritz, L., P. Kirchhof, M.R. Franz, D. Nuyens, T. Rossenbacker, A. Ottenhof, W. Haverkamp, G. Breithardt, E. Carmeliet, and P. Carmeliet, Effect of pacing and mexiletine on dispersion of repolarisation and arrhythmias in DeltaKPQ SCN5A(long QT3) mice. Cardiovasc Res,2003.57(4):1085-93.
[136]Schwartz, P.J., S.G Priori, M. Cerrone, C. Spazzolini, A. Odero, C. Napolitano, R. Bloise, GM. De Ferrari, C. Klersy, A.J. Moss, W. Zareba, J.L. Robinson, W.J. Hall, P.A. Brink, L. Toivonen, A.E. Epstein, C. Li, and D. Hu, Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome. Circulation,2004.109(15):1826-33.
[137]Benson, D.W., D.W. Wang, M. Dyment, T.K. Knilans, F.A. Fish, M.J. Strieper, T.H. Rhodes, and A.L. George, Jr., Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest,2003.112(7):1019-28.
[138]Lei, M., C.L. Huang, and Y. Zhang, Genetic Na+ channelopathies and sinus node dysfunction. Prog Biophys Mol Biol,2008.98(2-3):171-8.
[139]Makiyama, T., M. Akao, K. Tsuji, T. Doi, S. Ohno, K. Takenaka, A. Kobori, T. Ninomiya, H. Yoshida, M. Takano, N. Makita, F. Yanagisawa, Y. Higashi, Y. Takeyama, T. Kita, and M. Horie, High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations. J Am Coll Cardiol,2005.46(11):2100-6.
[140]Probst, V., F. Kyndt, F. Potet, J.N. Trochu, G. Mialet, S. Demolombe, J.J. Schott, I. Baro, D. Escande, and H. Le Marec, Haploinsufficiency in combination with aging causes SCN5A-linked hereditary Lenegre disease. J Am Coll Cardiol,2003.41(4):643-52.
[141]Schott, J.J., C. Alshinawi, F. Kyndt, V. Probst, T.M. Hoorntje, M. Hulsbeek, A.A. Wilde, D. Escande, M.M. Mannens, and H. Le Marec, Cardiac conduction defects associate with mutations in SCN5A. Nat Genet,1999. 23(1):20-1.
[142]Tan, H.L., M.T. Bink-Boelkens, C.R. Bezzina, P.C. Viswanathan, GC. Beaufort-Krol, P.J. van Tintelen, M.P. van den Berg, A.A. Wilde, and J.R. Balser, A sodium-channel mutation causes isolated cardiac conduction disease. Nature,2001.409(6823):1043-7.
[143]Makita, N., Phenotypic overlap of cardiac sodium channelopathies: individual-specific or mutation-specific? Circ J,2009.73(5):810-7.
[144]Veldkamp, M.W., R. Wilders, A. Baartscheer, J.G Zegers, C.R. Bezzina, and A.A. Wilde, Contribution of sodium channel mutations to bradycardia and sinus node dysfunction in LQT3 families. Circ Res,2003.92(9):976-83.
[145]Grant, A.O., M.P. Carboni, V. Neplioueva, C.F. Starmer, M. Memmi, C. Napolitano, and S. Priori, Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation. J Clin Invest,2002.110(8):1201-9.
[146]Priori, S.G, C. Napolitano, P.J. Schwartz, R. Bloise, L. Crotti, and E. Ronchetti, The elusive link between LQT3 and Brugada syndrome:the role of flecainide challenge. Circulation,2000.102(9):945-7.
[147]Olson, T.M., V.V. Michels, J.D. Ballew, S.P. Reyna, M.L. Karst, K.J. Herron, S.C. Horton, R.J. Rodeheffer, and J.L. Anderson, Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA,2005.293(4): 447-54.
[148]Chen, L.Y., J.D. Ballew, K.J. Herron, R.J. Rodeheffer, and T.M. Olson, A common polymorphism in SCN5A is associated with lone atrial fibrillation. Clin Pharmacol Ther,2007.81(1):35-41.
[149]Ellinor, P.T., E.G. Nam, M.A. Shea, D.J. Milan, J.N. Ruskin, and C.A. MacRae, Cardiac sodium channel mutation in atrial fibrillation. Heart Rhythm,2008. 5(1):99-105.
[150]Kusano, K.F., M. Taniyama, K. Nakamura, D. Miura, K. Banba, S. Nagase, H. Morita, N. Nishii, A. Watanabe, T. Tada, M. Murakami, K. Miyaji, S. Hiramatsu, K. Nakagawa, M. Tanaka, A. Miura, H. Kimura, S. Fuke, W. Sumita, S. Sakuragi, S. Urakawa, J. Iwasaki, and T. Ohe, Atrial fibrillation in patients with Brugada syndrome relationships of gene mutation., electrophysiology, and clinical backgrounds. J Am Coll Cardiol,2008.51(12): 1169-75.
[151]Li, Q., H. Huang, G. Liu, K. Lam, J. Rutberg, M.S. Green, D.H. Birnie, R. Lemery, M. Chahine, and M.H. Gollob, Gain-of-function mutation of Navl.5 in atrial fibrillation enhances cellular excitability and lowers the threshold for action potential firing. Biochem Biophys Res Commun,2009.380(1):132-7.
[152]Makiyama, T., M. Akao, S. Shizuta, T. Doi, K. Nishiyama, Y. Oka, S. Ohno, Y. Nishio, K. Tsuji, H. Itoh, T. Kimura, T. Kita, and M. Horie, A novel SCN5A gain-of-function mutation M1875T associated with familial atrial fibrillation. J Am Coll Cardiol,2008.52(16):1326-34.
[153]Benito, B., R. Brugada, R.M. Perich, E. Lizotte, J. Cinca, L. Mont, A. Berruezo, J.M. Tolosana, X. Freixa, P. Brugada, and J. Brugada, A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation. Heart Rhythm,2008.5(10):1434-40.
[154]Schwartz, P.J., M. Stramba-Badiale, A. Segantini, P. Austoni, G. Bosi, R. Giorgetti, F. Grancini, E.D. Marni, F. Perticone, D. Rosti, and P. Salice, Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med,1998.338(24):1709-14.
[155]Schwartz, P.J., S.G. Priori, R. Dumaine, C. Napolitano, C. Antzelevitch, M. Stramba-Badiale, T.A. Richard, M.R. Berti, and R. Bloise, A molecular link between the sudden infant death syndrome and the long-QT syndrome. N Engl J Med,2000.343(4):262-7.
[156]Arnestad, M., L. Crotti, T.O. Rognum, R. Insolia, M. Pedrazzini, C. Ferrandi, A. Vege, D.W. Wang, T.E. Rhodes, A.L. George, Jr., and P.J. Schwartz, Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation,2007.115(3):361-7.
[157]Wang, D.W., R.R. Desai, L. Crotti, M. Arnestad, R. Insolia, M. Pedrazzini, C. Ferrandi, A. Vege, T. Rognum, P.J. Schwartz, and A.L. George, Jr., Cardiac sodium channel dysfunction in sudden infant death syndrome. Circulation, 2007.115(3):368-76.
[158]Otagiri, T., K. Kijima, M. Osawa, K. Ishii, N. Makita, R. Matoba, K. Umetsu, and K. Hayasaka, Cardiac ion channel gene mutations in sudden infant death syndrome. Pediatr Res,2008.64(5):482-7.
[159]Probst, V., I. Denjoy, P.G Meregalli, J.C. Amirault, F. Sacher, J. Mansourati, D. Babuty, E. Villain, J. Victor, J.J. Schott, J.M. Lupoglazoff, P. Mabo, C. Veltmann, L. Jesel, P. Chevalier, S.A. Clur, M. Haissaguerre, C. Wolpert, H. Le Marec, and A.A. Wilde, Clinical aspects and prognosis of Brugada syndrome in children. Circulation,2007.115(15):2042-8.
[160]McNair, W.P., L. Ku, M.R. Taylor, P.R. Fain, D. Dao, E. Wolfel, and L. Mestroni, SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation,2004.110(15):2163-7.
[161]Ge, J., A. Sun, V. Paajanen, S. Wang, C. Su, Z. Yang, Y. Li, J. Jia, K. Wang, Y. Zou, L. Gao, and Z. Fan, Molecular and clinical characterization of a novel SCN5A mutation associated with atrioventricular block and dilated cardiomyopathy. Circ Arrhythm Electrophysiol,2008.1(2):83-92.
[162]Nguyen, T.P., D.W. Wang, T.H. Rhodes, and A.L. George, Jr., Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia. Circ Res,2008.102(3):364-71.
[163]Hesse, M., C.S. Kondo, R.B. Clark, L. Su, F.L. Allen, C.T. Geary-Joo, S. Kunnathu, D.L. Severson, A. Nygren, W.R. Giles, and J.C. Cross, Dilated cardiomyopathy is associated with reduced expression of the cardiac sodium channel Scn5a. Cardiovasc Res,2007.75(3):498-509.
[164]Ueda, K., C. Valdivia, A. Medeiros-Domingo, D.J. Tester, M. Vatta, G. Farrugia, M.J. Ackerman, and J.C. Makielski, Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc Natl Acad Sci U S A,2008.105(27):9355-60.
[165]Watanabe, H., D. Darbar, D.W. Kaiser, K. Jiramongkolchai, S. Chopra, B.S. Donahue, P.J. Kannankeril, and D.M. Roden, Mutations in sodium channel betal- and beta2-subunits associated with atrial fibrillation. Circ Arrhythm Electrophysiol,2009.2(3):268-75.
[166]Wang, P., Q. Yang, X. Wu, Y. Yang, L. Shi, C. Wang, G. Wu, Y. Xia, B. Yang, R. Zhang, C. Xu, X. Cheng, S. Li, Y. Zhao, F. Fu, Y. Liao, F. Fang, Q. Chen, X. Tu, and Q.K. Wang, Functional dominant-negative mutation of sodium channel subunit gene SCN3B associated with atrial fibrillation in a Chinese GeneID population. Biochem Biophys Res Commun.398(1):98-104.
[2]Viswanathan, P.C. and J.R. Balser, Inherited sodium channelopathies:a continuum of channel dysfunction. Trends Cardiovasc Med,2004.14(1): 28-35.
[3]Veldkamp, M.W., P.C. Viswanathan, C. Bezzina, A. Baartscheer, A.A. Wilde, and J.R. Balser, Two distinct congenital arrhythmias evoked by a multidysfunctional Na(+) channel. Circ Res,2000.86(9):E91-7.
[4]Wan, X., S. Chen, A. Sadeghpour, Q. Wang, and G.E. Kirsch, Accelerated inactivation in a mutant Na(+) channel associated with idiopathic ventricular fibrillation. Am J Physiol Heart Circ Physiol,2001.280(1):H354-60.
[5]Wang, D.W., P.C. Viswanathan, J.R. Balser, A.L. George, Jr., and D.W. Benson, Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation, 2002.105(3):341-6.
[6]Makielski, J.C. and A.L. Farley, Na(+) current in human ventricle: implications for sodium loading and homeostasis. J Cardiovasc Electrophysiol,2006.17 Suppl 1:S15-S20.
[7]Balser, J.R., Sodium "channelopathies" and sudden death:must you be so sensitive? Circ Res,1999.85(9):872-4.
[8]Matsuda, J.J., H. Lee, and E.F. Shibata, Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation. Circ Res,1992.70(1): 199-207.
[9]Matsuda, J.J., H.C. Lee, and E.F. Shibata, Acetylcholine reversal of isoproterenol-stimulated sodium currents in rabbit ventricular myocytes. Circ Res,1993.72(3):517-25.
[10]Sen, L., Y. Sakaguchi, and G. Cui, G protein modulates thyroid hormone-induced Na(+) channel activation in ventricular myocytes. Am J Physiol Heart Circ Physiol,2002.283(5):H2119-29.
[11]Shang, L.L., S. Sanyal, A.E. Pfahnl, Z. Jiao, J. Allen, H. Liu, and S.C. Dudley, Jr., NF-kappaB-dependent transcriptional regulation of the cardiac scn5a sodium channel by angiotensin Ⅱ. Am J Physiol Cell Physiol,2008.294(1): C372-9.
[12]Goldin, A.L., Resurgence of sodium channel research. Annu Rev Physiol, 2001.63:871-94.
[13]Haufe, V., J.A. Camacho, R. Dumaine, B. Gunther, C. Bollensdorff, G.S. von Banchet, K. Benndorf, and T. Zimmer, Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. J Physiol,2005.564(Pt 3):683-96.
[14]Kaufmann, S.G., R.E. Westenbroek, C. Zechner, A.H. Maass, S. Bischoff, J. Muck, E. Wischmeyer, T. Scheuer, and S.K. Maier, Functional protein expression of multiple sodium channel alpha- and beta-subunit isoforms in neonatal cardiomyocytes. J Mol Cell Cardiol,2009.48(1):261-9.
[15]Brette, F. and C.H. Orchard, No apparent requirement for neuronal sodium channels in excitation-contraction coupling in rat ventricular myocytes. Circ Res,2006.98(5):667-74.
[16]Maier, S.K., R.E. Westenbroek, K.A. McCormick, R. Curtis, T. Scheuer, and W.A. Catterall, Distinct subcellular localization of different sodium channel alpha and beta subunits in single ventricular myocytes from mouse heart. Circulation,2004.109(11):1421-7.
[17]Maier, S.K., R.E. Westenbroek, K.A. Schenkman, E.O. Feigl, T. Scheuer, and W.A. Catterall, An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart. Proc Natl Acad Sci U S A,2002.99(6):4073-8.
[18]Dhar Malhotra, J., C. Chen, I. Rivolta, H. Abriel, R. Malhotra, L.N. Mattei, F.C. Brosius, R.S. Kass, and L.L. Isom, Characterization of sodium channel alpha- and beta-subunits in rat and mouse cardiac myocytes. Circulation, 2001.103(9):1303-10.
[19]Fahmi, A.I., M. Patel, E.B. Stevens, A.L. Fowden, J.E. John,3rd, K. Lee, R. Pinnock, K. Morgan, A.P. Jackson, and J.I. Vandenberg, The sodium channel beta-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart. J Physiol,2001.537(Pt 3):693-700.
[20]Johnson, D. and E.S. Bennett, Isoform-specific effects of the beta2 subunit on voltage-gated sodium channel gating. J Biol Chem,2006.281(36): 25875-81.
[21]Ko, S.H., P.W. Lenkowski, H.C. Lee, J.P. Mounsey, and M.K. Patel, Modulation of Na(v)1.5 by betal-- and beta3-subunit co-expression in mammalian cells. Pflugers Arch,2005.449(4):403-12.
[22]Zimmer, T. and K. Benndorf, The intracellular domain of the beta 2 subunit modulates the gating of cardiac Na v 1.5 channels. Biophys J,2007.92(11): 3885-92.
[23]Liang, H.M., M. Tang, C.J. Liu, H.Y. Luo, Y.L. Song, X.W. Hu, J.Y. Xi, L.L. Gao, B. Nie, S.Y. Li, L.L. Lai, and J. Hescheler, Muscarinic cholinergic regulation of L-type calcium channel in heart of embryonic mice at different developmental stages. Acta Pharmacol Sin,2004.25(11):1450-7.
[24]Song, GL., M. Tang, C.J. Liu, H.Y. Luo, H.M. Liang, X.W. Hu, J.Y. Xi, L.L. Gao, B. Fleischmann, and J. Hescheler, Developmental changes in functional expression and beta-adrenergic regulation of I(f) in the heart of mouse embryo. Cell Res,2002.12(5-6):385-94.
[25]Davies, M.P., R.H. An, P. Doevendans, S. Kubalak, K.R. Chien, and R.S. Kass, Developmental changes in ionic channel activity in the embryonic murine heart. Circ Res,1996.78(1):15-25.
[26]Liu, W., K. Yasui, A. Arai, K. Kamiya, J. Cheng, I. Kodama, and J. Toyama, beta-adrenergic modulation of L-type Ca2+ channel currents in early-stage embryonic mouse heart. Am J Physiol,1999.276(2 Pt 2):H608-13.
[27]Yasui, K., W. Liu, T. Opthof, K. Kada, J.K. Lee, K. Kamiya, and I. Kodama, I(f) current and spontaneous activity in mouse embryonic ventricular myocytes. Circ Res,2001.88(5):536-42.
[28]Attwell, D., I. Cohen, D. Eisner, M. Ohba, and C. Ojeda, The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres. Pflugers Arch,1979.379(2):137-42.
[29]Baruscotti, M., D. DiFrancesco, and R.B. Robinson, A TTX-sensitive inward sodium current contributes to spontaneous activity in newborn rabbit sino-atrial node cells. J Physiol,1996.492 (Pt 1):21-30.
[30]Saint, D.A., The cardiac persistent sodium current:an appealing therapeutic target? Br J Pharmacol,2008.153(6):1133-42.
[31]Yokoshiki, H. and N. Tohse, Developmental Changes of Ion Channels., in Heart Physiology and Pathophysiology (Fourth Edition), N. Sperelakis, Y. Kurachi, A. Terzic, and M.V. Cohen, Editors.2001, Academic Press:New York. p.719-735.
[32]Bohle, T. and K. Benndorf, Voltage-dependent properties of three different gating modes in single cardiac Na+ channels. Biophys J,1995.69(3): 873-82.
[33]Bohle, T., M. Steinbis, C. Biskup, R. Koopmann, and K. Benndorf, Inactivation of single cardiac Na+ channels in three different gating modes. Biophys J,1998.75(4):1740-8.
[34]Nguyen, T.P., D.W. Wang, T.H. Rhodes, and A.L. George, Jr., Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia. Circ Res,2008.102(3):364-71.
[35]Lei, M., S.A. Jones, J. Liu, M.K. Lancaster, S.S. Fung, H. Dobrzynski, P. Camelliti, S.K. Maier, D. Noble, and M.R. Boyett, Requirement of neuronal-and cardiac-type sodium channels for murine sinoatrial node pacemaking. J Physiol,2004.559(Pt 3):835-48.
[36]Haufe, V, J.M. Cordeiro, T. Zimmer, Y.S. Wu, S. Schiccitano, K. Benndorf, and R. Dumaine, Contribution of neuronal sodium channels to the cardiac fast sodium current INa is greater in dog heart Purkinje fibers than in ventricles. Cardiovasc Res,2005.65(1):117-27.
[37]Dominguez, J.N., F. Navarro, D. Franco, R.P. Thompson, and A.E. Aranega, Temporal and spatial expression pattern of betal sodium channel subunit during heart development. Cardiovasc Res,2005.65(4):842-50.
[38]Baroudi, G., E. Carbonneau, V. Pouliot, and M. Chahine, SCN5A mutation (T1620M) causing Brugada syndrome exhibits different phenotypes when expressed in Xenopus oocytes and mammalian cells. FEBS Lett,2000. 467(1):12-6.
[39]Nuss, H.B., N. Chiamvimonvat, M.T. Perez-Garcia, G.F. Tomaselli, and E. Marban, Functional association of the beta 1 subunit with human cardiac (hH1) and rat skeletal muscle (mu 1) sodium channel alpha subunits expressed in Xenopus oocytes. J Gen Physiol,1995.106(6):1171-91.
[1]Wichter, T., E. Schulze-Bahr, L. Eckardt, M. Paul, B. Levkau, M. Meyborg, M. Schafers, W. Haverkamp, and G Breithardt, Molecular mechanisms of inherited ventricular arrhythmias. Herz,2002.27(8):712-39.
[2]Viswanathan, P.C. and J.R. Balser, Inherited sodium channelopathies:a continuum of channel dysfunction. Trends Cardiovasc Med,2004.14(1): 28-35.
[3]Veldkamp, M.W., P.C. Viswanathan, C. Bezzina, A. Baartscheer, A.A. Wilde, and J.R. Balser, Two distinct congenital arrhythmias evoked by a multidysfunctional Na(+) channel. Circ Res,2000.86(9):E91-7.
[4]Wan, X., S. Chen, A. Sadeghpour, Q. Wang, and GE. Kirsch, Accelerated inactivation in a mutant Na(+) channel associated with idiopathic ventricular fibrillation. Am J Physiol Heart Circ Physiol,2001.280(1):H354-60.
[5]Wang, D.W., P.C. Viswanathan, J.R. Balser, A.L. George, Jr., and D.W. Benson, Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation, 2002.105(3):341-6.
[6]Makielski, J.C. and A.L. Farley, Na(+) current in human ventricle: implications for sodium loading and homeostasis. J Cardiovasc Electrophysiol,2006.17 Suppl 1:S15-S20.
[7]Balser, J.R., Sodium "channelopathies" and sudden death:must you be so sensitive? Circ Res,1999.85(9):872-4.
[8]Matsuda, J.J., H. Lee, and E.F. Shibata, Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation. Circ Res,1992.70(1): 199-207.
[9]Matsuda, J.J., H.C. Lee, and E.F. Shibata, Acetylcholine reversal of isoproterenol-stimulated sodium currents in rabbit ventricular myocytes. Circ Res,1993.72(3):517-25.
[10]Sen, L., Y. Sakaguchi, and G. Cui, G protein modulates thyroid hormone-induced Na(+) channel activation in ventricular myocytes. Am J Physiol Heart Circ Physiol,2002.283(5):H2119-29.
[11]Shang, L.L., S. Sanyal, A.E. Pfahnl, Z. Jiao, J. Allen, H. Liu, and S.C. Dudley, Jr., NF-kappaB-dependent transcriptional regulation of the cardiac scn5a sodium channel by angiotensin Ⅱ. Am J Physiol Cell Physiol,2008.294(1): C372-9.
[12]Goldin, A.L., Resurgence of sodium channel research. Annu Rev Physiol, 2001.63:871-94.
[13]Haufe, V., J.A. Camacho, R. Dumaine, B. Gunther, C. Bollensdorff, G.S. von Banchet, K. Benndorf, and T. Zimmer, Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. J Physiol,2005.564(Pt 3):683-96.
[14]Kaufmann, S.G., R.E. Westenbroek, C. Zechner, A.H. Maass, S. Bischoff, J. Muck, E. Wischmeyer, T. Scheuer, and S.K. Maier, Functional protein expression of multiple sodium channel alpha- and beta-subunit isoforms in neonatal cardiomyocytes. J Mol Cell Cardiol,2009.48(1):261-9.
[15]Brette, F. and C.H. Orchard, No apparent requirement for neuronal sodium channels in excitation-contraction coupling in rat ventricular myocytes. Circ Res,2006.98(5):667-74.
[16]Maier, S.K., R.E. Westenbroek, K.A. McCormick, R. Curtis, T. Scheuer, and W.A. Catterall, Distinct subcellular localization of different sodium channel alpha and beta subunits in single ventricular myocytes from mouse heart. Circulation,2004.109(11):1421-7.
[17]Maier, S.K., R.E. Westenbroek, K.A. Schenkman, E.O. Feigl, T. Scheuer, and W.A. Catterall, An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart. Proc Natl Acad Sci U S A,2002.99(6):4073-8.
[18]Dhar Malhotra, J., C. Chen, I. Rivolta, H. Abriel, R. Malhotra, L.N. Mattei, F.C. Brosius, R.S. Kass, and L.L. Isom, Characterization of sodium channel alpha-and beta-subunits in rat and mouse cardiac myocytes. Circulation, 2001.103(9):1303-10.
[19]Fahmi, A.I., M. Patel, E.B. Stevens, A.L. Fowden, J.E. John,3rd, K. Lee, R. Pinnock, K. Morgan, A.P. Jackson, and J.I. Vandenberg, The sodium channel beta-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart. J Physiol,2001.537(Pt 3):693-700.
[20]Johnson, D. and E.S. Bennett, Isoform-specific effects of the beta2 subunit on voltage-gated sodium channel gating. J Biol Chem,2006.281(36): 25875-81.
[21]Ko, S.H., P.W. Lenkowski, H.C. Lee, J.P. Mounsey, and M.K. Patel, Modulation of Na(v)1.5 by betal-- and beta3-subunit co-expression in mammalian cells. Pflugers Arch,2005.449(4):403-12.
[22]Zimmer, T. and K. Benndorf, The intracellular domain of the beta 2 subunit modulates the gating of cardiac Na v 1.5 channels. Biophys J,2007.92(11): 3885-92.
[23]Liang, H.M., M. Tang, C.J. Liu, H.Y. Luo, Y.L. Song, X.W. Hu, J.Y. Xi, L.L. Gao, B. Nie, S.Y. Li, L.L. Lai, and J. Hescheler, Muscarinic cholinergic regulation of L-type calcium channel in heart of embryonic mice at different developmental stages. Acta Pharmacol Sin,2004.25(11):1450-7.
[24]Song, G.L., M. Tang, C.J. Liu, H.Y. Luo, H.M. Liang, X.W. Hu, J.Y. Xi, L.L. Gao, B. Fleischmann, and J. Hescheler, Developmental changes in functional expression and beta-adrenergic regulation of I(f) in the heart of mouse embryo. Cell Res,2002.12(5-6):385-94.
[25]Davies, M.P., R.H. An, P. Doevendans, S. Kubalak, K.R. Chien, and R.S. Kass, Developmental changes in ionic channel activity in the embryonic murine heart. Circ Res,1996.78(1):15-25.
[26]Liu, W., K. Yasui, A. Arai, K. Kamiya, J. Cheng, I. Kodama, and J. Toyama, beta-adrenergic modulation of L-type Ca2+-channel currents in early-stage embryonic mouse heart. Am J Physiol,1999.276(2 Pt 2):H608-13.
[27]Yasui, K., W. Liu, T. Opthof, K. Kada, J.K. Lee, K. Kamiya, and I. Kodama, I(f) current and spontaneous activity in mouse embryonic ventricular myocytes. Circ Res,2001.88(5):536-42.
[28]Attwell, D., I. Cohen, D. Eisner, M. Ohba, and C. Ojeda, The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres. Pflugers Arch,1979.379(2):137-42.
[29]Baruscotti, M., D. DiFrancesco, and R.B. Robinson, A TTX-sensitive inward sodium current contributes to spontaneous activity in newborn rabbit sino-atrial node cells. J Physiol,1996.492 (Pt 1):21-30.
[30]Saint, D.A., The cardiac persistent sodium current:an appealing therapeutic-target? Br J Pharmacol,2008.153(6):1133-42.
[31]Yokoshiki, H. and N. Tohse, Developmental Changes of Ion Channels., in Heart Physiology and Pathophysiology (Fourth Edition), N. Sperelakis, Y. Kurachi, A. Terzic, and M.V. Cohen, Editors.2001, Academic Press:New York. p.719-735.
[32]Bohle, T. and K. Benndorf, Voltage-dependent properties of three different gating modes in single cardiac Na+ channels. Biophys J,1995.69(3): 873-82.
[33]Bohle, T., M. Steinbis, C. Biskup, R. Koopmann, and K. Benndorf, Inactivation of single cardiac Na+ channels in three different gating modes. Biophys J,1998.75(4):1740-8.
[34]Nguyen, T.P., D.W. Wang, T.H. Rhodes, and A.L. George, Jr., Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia. Circ Res,2008.102(3):364-71.
[35]Lei, M., S.A. Jones, J. Liu, M.K. Lancaster, S.S. Fung, H. Dobrzynski, P. Camelliti, S.K. Maier, D. Noble, and M.R. Boyett, Requirement of neuronal-and cardiac-type sodium channels for murine sinoatrial node pacemaking. J Physiol,2004.559(Pt 3):835-48.
[36]Haufe, V., J.M. Cordeiro, T. Zimmer, Y.S. Wu, S. Schiccitano, K. Benndorf, and R. Dumaine, Contribution of neuronal sodium channels to the cardiac fast sodium current INa is greater in dog heart Purkinje fibers than in ventricles. Cardiovasc Res,2005.65(1):117-27.
[37]Dominguez, J.N., F. Navarro, D. Franco, R.P. Thompson, and A.E. Aranega, Temporal and spatial expression pattern of betal sodium channel subunit during heart development. Cardiovasc Res,2005.65(4):842-50.
[38]Baroudi, G, E. Carbonneau, V. Pouliot, and M. Chahine, SCN5A mutation (T1620M) causing Brugada syndrome exhibits different phenotypes when expressed in Xenopus oocytes and mammalian cells. FEBS Lett,2000. 467(1):12-6.
[39]Nuss, H.B., N. Chiamvimonvat, M.T. Perez-Garcia, G.F. Tomaselli, and E. Marban, Functional association of the beta 1 subunit with human cardiac (hH1) and rat skeletal muscle (mu 1) sodium channel alpha subunits expressed in Xenopus oocytes. J Gen Physiol,1995.106(6):1171-91.
[1]Catterall, W.A., From ionic currents to molecular mechanisms:the structure and function of voltage-gated sodium channels. Neuron,2000.26(1):13-25.
[2]Goldin, A.L., R.L. Barchi, J.H. Caldwell, F. Hofmann, J.R. Howe, J.C. Hunter, R.G Kallen, G. Mandel, M.H. Meisler, Y.B. Netter, M. Noda, M.M. Tamkun, S.G. Waxman, J.N. Wood, and W.A. Catterall, Nomenclature of voltage-gated sodium channels. Neuron,2000.28(2):365-8.
[3]Kaufmann, S.G, R.E. Westenbroek, C. Zechner, A.H. Maass, S. Bischoff, J. Muck, E. Wischmeyer, T. Scheuer, and S.K. Maier, Functional protein expression of multiple sodium channel alpha-and beta-subunit isoforms in neonatal cardiomyocytes. J Mol Cell Cardiol,2010.48(1):261-9.
[4]Haufe, V., J.A. Camacho, R. Dumaine, B. Gunther, C. Bollensdorff, G.S. von Banchet, K. Benndorf, and T. Zimmer, Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. J Physiol,2005.564(Pt 3):683-96.
[5]Makielski, J.C., B. Ye, C.R. Valdivia, M.D. Pagel, J. Pu, D.J. Tester, and M.J. Ackerman, A ubiquitous splice variant and a common polymorphism affect heterologous expression of recombinant human SCN5A heart sodium channels. Circ Res,2003.93(9):821-8.
[6]Abriel, H. and R.S. Kass, Regulation of the voltage-gated cardiac sodium channel Nav1.5 by interacting proteins. Trends Cardiovasc Med,2005.15(1): 35-40.
[7]Hu, D., H. Barajas-Martinez, E. Burashnikov, M. Springer, Y. Wu, A. Varro, R. Pfeiffer, T.T. Koopmann, J.M. Cordeiro, A. Guerchicoff, G.D. Pollevick, and C. Antzelevitch, A mutation in the beta 3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype. Circ Cardiovasc Genet,2009.2(3): 270-8.
[8]Ko, S.H., P.W. Lenkowski, H.C. Lee, J.P. Mounsey, and M.K. Patel, Modulation of Na(v)1.5 by betal-- and beta3-subunit co-expression in mammalian cells. Pflugers Arch,2005.449(4):403-12.
[9]Medeiros-Domingo, A., T. Kaku, D.J. Tester, P. Iturralde-Torres, A. Itty, B. Ye, C. Valdivia, K. Ueda, S. Canizales-Quinteros, M.T. Tusie-Luna, J.C. Makielski, and M.J. Ackerman, SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome. Circulation,2007.116(2):134-42.
[10]Watanabe, H., T.T. Koopmann, S. Le Scouarnec, T. Yang, C.R. Ingram, J.J. Schott, S. Demolombe, V. Probst, F. Anselme, D. Escande, A.C. Wiesfeld, A. Pfeufer, S. Kaab, H.E. Wichmann, C. Hasdemir, Y. Aizawa, A.A. Wilde, D.M. Roden, and C.R. Bezzina, Sodium channel betal subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest,2008.118(6):2260-8.
[11]Dhar Malhotra, J., C. Chen, I. Rivolta, H. Abriel, R. Malhotra, L.N. Mattei, F.C. Brosius, R.S. Kass, and L.L. Isom, Characterization of sodium channel alpha-and beta-subunits in rat and mouse cardiac myocytes. Circulation,2001. 103(9):1303-10.
[12]Yu, F.H., R.E. Westenbroek, I. Silos-Santiago, K.A. McCormick, D. Lawson, P. Ge, H. Ferriera, J. Lilly, P.S. DiStefano, W.A. Catterall, T. Scheuer, and R, Curtis, Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2. J Neurosci,2003.23(20):7577-85.
[13]Isom, L.L., D.S. Ragsdale, K.S. De Jongh, R.E. Westenbroek, B.F. Reber, T. Scheuer, and W.A. Catterall, Structure and function of the beta 2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell, 1995.83(3):433-42.
[14]Johnson, D. and E.S. Bennett, Isoform-specific effects of the beta2 subunit on voltage-gated sodium channel gating. J Biol Chem,2006.281(36):25875-81.
[15]Zimmer, T. and K. Benndorf, The intracellular domain of the beta 2 subunit modulates the gating of cardiac Na v 1.5 channels. Biophys J,2007.92(11): 3885-92.
[16]Fahmi, A.I., M. Patel, E.B. Stevens, A.L. Fowden, J.E. John,3rd, K. Lee, R. Pinnock, K. Morgan, A.P. Jackson, and J.I. Vandenberg, The sodium channel beta-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart. J Physiol,2001.537(Pt 3):693-700.
[17]Malhotra, J.D., K. Kazen-Gillespie, M. Hortsch, and L.L. Isom, Sodium channel beta subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact. J Biol Chem,2000.275(15):11383-8.
[18]Srinivasan, J., M. Schachner, and W.A. Catterall, Interaction of voltage-gated sodium channels with the extracellular matrix molecules tenascin-C and tenascin-R. Proc Natl Acad Sci U S A,1998.95(26):15753-7.
[19]Chioni, A.M., W.J. Brackenbury, J.D. Calhoun, L.L. Isom, and M.B. Djamgoz, A novel adhesion molecule in human breast cancer cells:voltage-gated Na+ channel betal subunit. Int J Biochem Cell Biol,2009.41(5):1216-27.
[20]Malhotra, J.D., M.C. Koopmann, K.A. Kazen-Gillespie, N. Fettman, M. Hortsch, and L.L. Isom, Structural requirements for interaction of sodium channel beta 1 subunits with ankyrin. J Biol Chem,2002.277(29):26681-8.
[21]Malhotra, J.D., V. Thyagarajan, C. Chen, and L.L. Isom, Tyrosine-phosphorylated and nonphosphorylated sodium channel beta1 subunits are differentially localized in cardiac myocytes. J Biol Chem,2004. 279(39):40748-54.
[22]Cohen, S.A., Immunocytochemical localization of rH1 sodium channel in adult rat heart atria and ventricle. Presence in terminal intercalated disks. Circulation,1996.94(12):3083-6.
[23]Maier, S.K., R.E. Westenbroek, K.A. McCormick, R. Curtis, T. Scheuer, and W.A. Catterall, Distinct subcellular localization of different sodium channel alpha and beta subunits in single ventricular myocytes from mouse heart. Circulation,2004.109(11):1421-7.
[24]Brette, F. and C.H. Orchard, Density and sub-cellular distribution of cardiac and neuronal sodium channel isoforms in rat ventricular myocytes. Biochem Biophys Res Commun,2006.348(3):1163-6.
[25]Baba, S., W. Dun, C. Cabo, and P.A. Boyden, Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia. Circulation,2005.112(16):2386-96.
[26]Mohler, P.J., I. Splawski, C. Napolitano, G. Bottelli, L. Sharpe, K. Timothy, S.G. Priori, M.T. Keating, and V. Bennett, A cardiac arrhythmia syndrome caused by loss of ankyrin-B function. Proc Natl Acad Sci U S A,2004. 101(24):9137-42.
[27]Zimmer, T., C. Biskup, S. Dugarmaa, F. Vogel, M. Steinbis, T. Bohle, Y.S. Wu, R. Dumaine, and K. Benndorf, Functional expression of GFP-linked human heart sodium channel (hH1) and subcellular localization of the a subunit in HEK293 cells and dog cardiac myocytes. J Membr Biol,2002.186(1):1-12.
[28]Tateyama, M., H. Liu, A.S. Yang, J.W. Cormier, and R.S. Kass, Structural effects of an LQT-3 mutation on heart Na+ channel gating. Biophys J,2004. 86(3):1843-51.
[29]Coraboeuf, E., E. Deroubaix, and A. Coulombe, Effect of tetrodotoxin on action potentials of the conducting system in the dog heart. Am J Physiol, 1979.236(4):H561-7.
[30]Hodgkin, A.L. and A.F. Huxley, A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol, 1952.117(4):500-44.
[31]Armstrong, C.M., Sodium channels and gating currents. Physiol Rev,1981. 61(3):644-83.
[32]Stuhmer, W., F. Conti, H. Suzuki, X.D. Wang, M. Noda, N. Yahagi, H. Kubo, and S. Numa, Structural parts involved in activation and inactivation of the sodium channel. Nature,1989.339(6226):597-603.
[33]Yang, N. and R. Horn, Evidence for voltage-dependent S4 movement in sodium channels. Neuron,1995.15(1):213-8.
[34]Armstrong, C.M., F. Bezanilla, and E. Rojas, Destruction of sodium conductance inactivation in squid axons perfused with pronase. J Gen Physiol., 1973.62(4):375-91.
[35]Armstrong, C.M. and F. Bezanilla, Inactivation of the sodium channel. II. Gating current experiments. J Gen Physiol,1977.70(5):567-90.
[36]Vassilev, P.M., T. Scheuer, and W.A. Catterall, Identification of an intracellular peptide segment involved in sodium channel inactivation. Science,1988. 241(4873):1658-61.
[37]Patton, D.E., J.W. West, W.A. Catterall, and A.L. Goldin, Amino acid residues required for fast Na(+)-channel inactivation:charge neutralizations and deletions in the III-IV linker. Proc Natl Acad Sci U S A,1992.89(22): 10905-9.
[38]West, J.W., D.E. Patton, T. Scheuer, Y. Wang, A.L. Goldin, and W.A. Catterall, A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation. Proc Natl Acad Sci U S A,1992.89(22):10910-4.
[39]Kellenberger, S., T. Scheuer, and W.A. Catterall, Movement of the Na+ channel inactivation gate during inactivation. J Biol Chem,1996.271(48): 30971-9.
[40]Matsuda, J.J., H. Lee, and E.F. Shibata, Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation. Circ Res,1992.70(1):199-207.
[41]Matsuda, J.J., H.C. Lee, and E.F. Shibata, Acetylcholine reversal of isoproterenol-stimulated sodium currents in rabbit ventricular myocytes. Circ Res,1993.72(3):517-25.
[42]Shang, L.L., S. Sanyal, A.E. Pfahnl, Z. Jiao, J. Allen, H. Liu, and S.C. Dudley, Jr., NF-kappaB-dependent transcriptional regulation of the cardiac scn5a sodium channel by angiotensin Ⅱ. Am J Physiol Cell Physiol,2008.294(1): C372-9.
[43]Boixel, C., B. Gavillet, J.S. Rougier, and H. Abriel, Aldosterone increases voltage-gated sodium current in ventricular myocytes. Am J Physiol Heart Circ Physiol,2006.290(6):H2257-66.
[44]Sen, L., Y. Sakaguchi, and G. Cui, G protein modulates thyroid hormone-induced Na(+) channel activation in ventricular myocytes. Am J Physiol Heart Circ Physiol,2002.283(5):H2119-29.
[45]Ahmmed, G.U., Y. Xu, P. Hong Dong, Z. Zhang, J. Eiserich, and N. Chiamvimonvat, Nitric oxide modulates cardiac Na(+) channel via protein kinase A and protein kinase G. Circ Res,2001.89(11):1005-13.
[46]Bers, D.M., Cardiac excitation-contraction coupling. Nature,2002.415(6868): 198-205.
[47]Ono, K., T. Kiyosue, and M. Arita, Isoproterenol, DBcAMP, and forskolin inhibit cardiac sodium current. Am J Physiol,1989.256(6 Pt 1):C1131-7.
[48]Schubert, B., A.M. VanDongen, G.E. Kirsch, and A.M. Brown, Beta-adrenergic inhibition of cardiac sodium channels by dual G-protein pathways. Science,1989.245(4917):516-9.
[49]Lu, T., H.C. Lee, J.A. Kabat, and E.F. Shibata, Modulation of rat cardiac sodium channel by the stimulatory G protein alpha subunit. J Physiol,1999. 518 (Pt 2):371-84.
[50]Baba, S., W. Dun, and P.A. Boyden, Can PKA activators rescue Na+ channel function in epicardial border zone cells that survive in the infarcted canine heart? Cardiovasc Res,2004.64(2):260-7.
[51]Zhou, J., J. Yi, N. Hu, A.L. George, Jr., and K.T. Murray, Activation of protein kinase A modulates trafficking of the human cardiac sodium channel in Xenopus oocytes. Circ Res,2000.87(1):33-8.
[52]Wagner, S., N. Dybkova, E.C. Rasenack, C. Jacobshagen, L. Fabritz, P. Kirchhof, S.K. Maier, T. Zhang, G. Hasenfuss, J.H. Brown, D.M. Bers, and L.S. Maier, Ca2+/calmodulin-dependent protein kinase Ⅱ regulates cardiac Na+ channels. J Clin Invest,2006.116(12):3127-38.
[53]Soderling, T.R., B. Chang, and D. Brickey, Cellular signaling through multifunctional Ca2+/calmodulin-dependent protein kinase Ⅱ. J Biol Chem, 2001.276(6):3719-22.
[54]Maier, L.S. and D.M. Bers, Calcium, calmodulin, and calcium-calmodulin kinase Ⅱ:heartbeat to heartbeat and beyond. J Mol Cell Cardiol,2002.34(8): 919-39.
[55]Davis, M.J., X. Wu, T.R. Nurkiewicz, J. Kawasaki, P. Gui, M.A. Hill, and E. Wilson, Regulation of ion channels by protein tyrosine phosphorylation. Am J Physiol Heart Circ Physiol,2001.281(5):H1835-62.
[56]Ahern, C.A., J.F. Zhang, M.J. Wookalis, and R. Horn, Modulation of the cardiac sodium channel NaV1.5 by Fyn, a Src family tyrosine kinase. Circ Res, 2005.96(9):991-8.
[57]Liu, H., H.Y. Sun, C.P. Lau, and G.R. Li, Regulation of voltage-gated cardiac sodium current by epidermal growth factor receptor kinase in guinea pig ventricular myocytes. J Mol Cell Cardiol,2007.42(4):760-8.
[58]Arad, M., C.E. Seidman, and J.G Seidman, AMP-activated protein kinase in the heart:role during health and disease. Circ Res,2007.100(4):474-88.
[59]Gollob, M.H., Glycogen storage disease as a unifying mechanism of disease in the PRKAG2 cardiac syndrome. Biochem Soc Trans,2003.31(Pt 1):228-31.
[60]Light, P.E., C.H. Wallace, and J.R. Dyck, Constitutively active adenosine monophosphate-activated protein kinase regulates voltage-gated sodium channels in ventricular myocytes. Circulation,2003.107(15):1962-5.
[61]Molkentin, J.D., Calcineurin-NFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs. Cardiovasc Res,2004. 63(3):467-75.
[62]Dong, D., Y. Duan, J. Guo, D.E. Roach, S.L. Swirp, L. Wang, J.P. Lees-Miller, R.S. Sheldon, J.D. Molkentin, and H.J. Duff, Overexpression of calcineurin in mouse causes sudden cardiac death associated with decreased density of K+ channels. Cardiovasc Res,2003.57(2):320-32.
[63]Guo, J., S. Zhan, J. Somers, R.E. Westenbroek, W.A. Catterall, D.E. Roach, R.S. Sheldon, J.P. Lees-Miller, P. Li, Y. Shimoni, and H.J. Duff, Decrease in density of INa is in the common final pathway to heart block in murine hearts overexpressing calcineurin. Am J Physiol Heart Circ Physiol,2006.291(6): H2669-79.
[64]Murray, K.T., N.N. Hu, J.R. Daw, H.G. Shin, M.T. Watson, A.B. Mashbum, and A.L. George, Jr., Functional effects of protein kinase C activation on the human cardiac Na+ channel. Circ Res,1997.80(3):370-6.
[65]Bennett, V. and A.J. Baines, Spectrin and ankyrin-based pathways:metazoan inventions for integrating cells into tissues. Physiol Rev,2001.81(3):1353-92.
[66]Lemaillet, G, B. Walker, and S. Lambert, Identification of a conserved ankyrin-binding motif in the family of sodium channel alpha subunits. J Biol Chem,2003.278(30):27333-9.
[67]Priori, S.G, C. Napolitano, M. Gasparini, C. Pappone, P. Della Bella, M. Brignole, U. Giordano, T. Giovannini, C. Menozzi, R. Bloise, L. Crotti, L. Terreni, and P.J. Schwartz, Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome:A prospective evaluation of 52 families. Circulation,2000.102(20):2509-15.
[68]Mohler, P.J., I. Rivolta, C. Napolitano, G. LeMaillet, S. Lambert, S.G. Priori, and V. Bennett, Navl.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Navl.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A,2004.101(50):17533-8.
[69]Mohler, P.J., J.J. Schott, A.O. Gramolini, K.W. Dilly, S. Guatimosim, W.H. duBell, L.S. Song, K. Haurogne, F. Kyndt, M.E. Ali, T.B. Rogers, W.J. Lederer, D. Escande, H. Le Marec, and V. Bennett, Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature,2003. 421(6923):634-9.
[70]Chauhan, V.S., S. Tuvia, M. Buhusi, V. Bennett, and A.O. Grant, Abnormal cardiac Na(+) channel properties and QT heart rate adaptation in neonatal ankyrin(B) knockout mice. Circ Res,2000.86(4):441-7.
[71]Baroudi, G, E. Carbonneau, V. Pouliot, and M. Chahine, SCN5A mutation (T1620M) causing Brugada syndrome exhibits different phenotypes when expressed in Xenopus oocytes and mammalian cells. FEBS Lett,2000.467(1): 12-6.
[72]Nuss, H.B., N. Chiamvimonvat, M.T. Perez-Garcia, GF. Tomaselli, and E. Marban, Functional association of the beta 1 subunit with human cardiac (hH1) and rat skeletal muscle (mu 1) sodium channel alpha subunits expressed in Xenopus oocytes. J Gen Physiol,1995.106(6):1171-91.
[73]Saimi, Y. and C. Kung, Calmodulin as an ion channel subunit. Annu Rev Physiol,2002.64:289-311.
[74]Herzog, R.I., C. Liu, S.G. Waxman, and T.R. Cummins, Calmodulin binds to the C terminus of sodium channels Nav1.4 and Navl.6 and differentially modulates their functional properties. J Neurosci,2003.23(23):8261-70.
[75]Deschenes, I., N. Neyroud, D. DiSilvestre, E. Marban, D.T. Yue, and GF. Tomaselli, Isoform-specific modulation of voltage-gated Na(+) channels by calmodulin. Circ Res,2002.90(4):E49-57.
[76]Kim, J., S. Ghosh, H. Liu, M. Tateyama, R.S. Kass, and GS. Pitt, Calmodulin mediates Ca2+ sensitivity of sodium channels. J Biol Chem,2004.279(43): 45004-12.
[77]Tan, H.L., S. Kupershmidt, R. Zhang, S. Stepanovic, D.M. Roden, A.A. Wilde, M.E. Anderson, and J.R. Balser, A calcium sensor in the sodium channel modulates cardiac excitability. Nature,2002.415(6870):442-7.
[78]Wingo, T.L., V.N. Shah, M.E. Anderson, T.P. Lybrand, W.J. Chazin, and J.R. Balser, An EF-hand in the sodium channel couples intracellular calcium to cardiac excitability. Nat Struct Mol Biol,2004.11(3):219-25.
[79]Motoike, H.K., H. Liu, I.W. Glaaser, A.S. Yang, M. Tateyama, and R.S. Kass, The Na+ channel inactivation gate is a molecular complex:a novel role of the COOH-terminal domain. J Gen Physiol,2004.123(2):155-65.
[80]Hicke, L. and R. Dunn, Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu Rev Cell Dev Biol,2003.19:141-72.
[81]Rotin, D., O. Staub, and R. Haguenauer-Tsapis, Ubiquitination and endocytosis of plasma membrane proteins:role of Nedd4/Rsp5p family of ubiquitin-protein ligases. J Membr Biol,2000.176(1):1-17.
[82]Staub, O. and D. Rotin, WW domains. Structure,1996.4(5):495-9.
[83]Fotia, A.B., J. Ekberg, D.J. Adams, D.I. Cook, P. Poronnik, and S. Kumar, Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2. J Biol Chem,2004.279(28):28930-5.
[84]Rougier, J.S., M.X. van Bemmelen, M.C. Bruce, T. Jespersen, B. Gavillet, F. Apotheloz, S. Cordonier, O. Staub, D. Rotin, and H. Abriel, Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins. Am J Physiol Cell Physiol,2005.288(3): C692-701.
[85]Abriel, H., E. Kamynina, J.D. Horisberger, and O. Staub, Regulation of the cardiac voltage-gated Na+ channel (H1) by the ubiquitin-protein ligase Nedd4. FEBS Lett,2000.466(2-3):377-80.
[86]van Bemmelen, M.X., J.S. Rougier, B. Gavillet, F. Apotheloz, D. Daidie, M. Tateyama, I. Rivolta, M.A. Thomas, R.S. Kass, O. Staub, and H. Abriel, Cardiac voltage-gated sodium channel Navl.5 is regulated by Nedd4-2 mediated ubiquitination. Circ Res,2004.95(3):284-91.
[87]Ingham, R.J., G. Gish, and T. Pawson, The Nedd4 family of E3 ubiquitin ligases:functional diversity within a common modular architecture. Oncogene, 2004.23(11):1972-84.
[88]Albrecht, D.E. and S.C. Froehner, Syntrophins and dystrobrevins:defining the dystrophin scaffold at synapses. Neurosignals,2002.11(3):123-9.
[89]Gee, S.H., R. Madhavan, S.R. Levinson, J.H. Caldwell, R. Sealock, and S.C. Froehner, Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins. J Neurosci,1998.18(1):128-37.
[90]Zhou, J., H.G Shin, J. Yi, W. Shen, C.P. Williams, and K.T. Murray, Phosphorylation and putative ER retention signals are required for protein kinase A-mediated potentiation of cardiac sodium current. Circ Res,2002. 91(6):540-6.
[91]Ou, Y., P. Strege, S.M. Miller, J. Makielski, M. Ackerman, S.J. Gibbons, and G Farrugia, Syntrophin gamma 2 regulates SCN5A gating by a PDZ domain-mediated interaction. J Biol Chem,2003.278(3):1915-23.
[92]Finsterer, J. and C. Stollberger, The heart in human dystrophinopathies. Cardiology,2003.99(1):1-19.
[93]Liu, C., S.D. Dib-Hajj, and S.G. Waxman, Fibroblast growth factor homologous factor 1B binds to the C terminus of the tetrodotoxin-resistant sodium channel rNav1.9a (NaN). J Biol Chem,2001.276(22):18925-33.
[94]Liu, C.J., S.D. Dib-Hajj, M. Renganathan, T.R. Cummins, and S.G. Waxman, Modulation of the cardiac sodium channel Navl.5 by fibroblast growth factor homologous factor 1B. J Biol Chem,2003.278(2):1029-36.
[95]Wehrens, X.H., H. Abriel, C. Cabo, J. Benhorin, and R.S. Kass, Arrhythmogenic mechanism of an LQT-3 mutation of the human heart Na(+) channel alpha-subunit:A computational analysis. Circulation,2000.102(5): 584-90.
[96]Brugada, P. and J. Brugada, Right bundle branch block, persistent ST segment elevation and sudden cardiac death:a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol,1992.20(6):1391-6.
[97]Miyazaki, T., H. Mitamura, S. Miyoshi, K. Soejima, Y. Aizawa, and S. Ogawa, Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. J Am Coll Cardiol,1996.27(5):1061-70.
[98]Wilde, A.A., C. Antzelevitch, M. Borggrefe, J. Brugada, R. Brugada, P. Brugada, D. Corrado, R.N. Hauer, R.S. Kass, K. Nademanee, S.G. Priori, and J.A. Towbin, Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation,2002.106(19):2514-9.
[99]Zimmer, T. and R. Surber, SCN5A channelopathies--an update on mutations and mechanisms. Prog Biophys Mol Biol,2008.98(2-3):120-36.
[100]Valdivia, C.R., D.J. Tester, B.A. Rok, C.B. Porter, T.M. Munger, A. Jahangir, J.C. Makielski, and M.J. Ackerman, A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs. Cardiovasc Res,2004. 62(1):53-62.
[101]Kyndt, F., V. Probst, F. Potet, S. Demolombe, J.C. Chevallier, I. Baro, J.P. Moisan, P. Boisseau, J.J. Schott, D. Escande, and H. Le Marec, Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family. Circulation,2001.104(25):3081-6.
[102]Amin, A.S., A.O. Verkerk, Z.A. Bhuiyan, A.A. Wilde, and H.L. Tan, Novel Brugada syndrome-causing mutation in ion-conducting pore of cardiac Na+ channel does not affect ion selectivity properties. Acta Physiol Scand,2005. 185(4):291-301.
[103]Bezzina, C., M.W. Veldkamp, M.P. van Den Berg, A.V. Postma, M.B. Rook, J.W. Viersma, I.M. van Langen, G. Tan-Sindhunata, M.T. Bink-Boelkens, A.H. van Der Hout, M.M. Mannens, and A.A. Wilde, A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res,1999. 85(12):1206-13.
[104]Dumaine, R., J.A. Towbin, P. Brugada, M. Vatta, D.V. Nesterenko, V.V. Nesterenko, J. Brugada, R. Brugada, and C. Antzelevitch, Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circ Res,1999.85(9):803-9.
[105]Smits, J.P., T.T. Koopmann, R. Wilders, M.W. Veldkamp, T. Opthof, Z.A. Bhuiyan, M.M. Mannens, J.R. Balser, H.L. Tan, C.R. Bezzina, and A.A. Wilde, A mutation in the human cardiac sodium channel (E161K) contributes to sick sinus syndrome, conduction disease and Brugada syndrome in two families. J Mol Cell Cardiol,2005.38(6):969-81.
[106]Smits, J.P., L. Eckardt, V. Probst, C.R. Bezzina, J.J. Schott, C.A. Remme, W. Haverkamp, G. Breithardt, D. Escande, E. Schulze-Bahr, H. LeMarec, and A.A. Wilde, Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. J Am Coll Cardiol,2002.40(2):350-6.
[107]Antzelevitch, C., Cellular basis for the repolarization waves of the ECG Ann N Y Acad Sci,2006.1080:268-81.
[108]Meregalli, P.G, A.A. Wilde, and H.L. Tan, Pathophysiological mechanisms of Brugada syndrome:depolarization disorder, repolarization disorder, or more? Cardiovasc Res,2005.67(3):367-78.
[109]Amin, A.S., P.G Meregalli, A. Bardai, A.A. Wilde, and H.L. Tan, Fever increases the risk for cardiac arrest in the Brugada syndrome. Ann Intern Med, 2008.149(3):216-8.
[110]Junttila, M.J., M. Gonzalez, E. Lizotte, B. Benito, K. Vernooy, A. Sarkozy, H.V. Huikuri, P. Brugada, J. Brugada, and R. Brugada, Induced Brugada-type electrocardiogram, a sign for imminent malignant arrhythmias. Circulation, 2008.117(14):1890-3.
[111]Matsuo, K., M. Akahoshi, S. Seto, and K. Yano, Disappearance of the Brugada-type electrocardiogram after surgical castration:a role for testosterone and an explanation for the male preponderance. Pacing Clin Electrophysiol,2003.26(7 Pt 1):1551-3.
[112]Shimizu, W., K. Matsuo, Y. Kokubo, K. Satomi, T. Kurita, T. Noda, N. Nagaya, K. Suyama, N. Aihara, S. Kamakura, N. Inamoto, M. Akahoshi, and H. Tomoike, Sex hormone and gender difference--role of testosterone on male predominance in Brugada syndrome. J Cardiovasc Electrophysiol,2007.18(4): 415-21.
[113]Postema, P.G, C. Wolpert, A.S. Amin, V. Probst, M. Borggrefe, D.M. Roden, S.G Priori, H.L. Tan, M. Hiraoka, J. Brugada, and A.A. Wilde, Drugs and Brugada syndrome patients:review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org). Heart Rhythm,2009.6(9): 1335-41.
[114]Brugada, J., P. Brugada, and R. Brugada, The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome. Europace,1999.1(3):156-66.
[115]Morita, H., J. Wu, and D.P. Zipes, The QT syndromes:long and short. Lancet, 2008.372(9640):750-63.
[116]Kapplinger, J.D., D.J. Tester, B.A. Salisbury, J.L. Carr, C. Harris-Kerr, G.D. Pollevick, A.A. Wilde, and M.J. Ackerman, Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm,2009.6(9): 1297-303.
[117]Wang, Q., J. Shen, I. Splawski, D. Atkinson, Z. Li, J.L. Robinson, A.J. Moss, J.A. Towbin, and M.T. Keating, SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell,1995.80(5):805-11.
[118]Bennett, P.B., K. Yazawa, N. Makita, and A.L. George, Jr., Molecular mechanism for an inherited cardiac arrhythmia. Nature,1995.376(6542): 683-5.
[119]Napolitano, C, S.G. Priori, P.J. Schwartz, R. Bloise, E. Ronchetti, J. Nastoli,G. Bottelli, M. Cerrone, and S. Leonardi, Genetic testing in the long QT syndrome:development and validation of an efficient approach to genotyping in clinical practice. JAMA,2005.294(23):2975-80.
[120]Tester, D.J., M.L. Will, C.M. Haglund, and M.J. Ackerman, Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm,2005.2(5):507-17.
[121]Potet, F., B. Chagot, M. Anghelescu, P.C. Viswanathan, S.Z. Stepanovic, S. Kupershmidt, W.J. Chazin, and J.R. Balser, Functional Interactions between Distinct Sodium Channel Cytoplasmic Domains through the Action of Calmodulin. J Biol Chem,2009.284(13):8846-54.
[122]Wang, D.W., K. Yazawa, A.L. George, Jr., and P.B. Bennett, Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome. Proc Natl Acad Sci U S A,1996.93(23):13200-5.
[123]Wedekind, H., J.P. Smits, E. Schulze-Bahr, R. Arnold, M.W. Veldkamp, T. Bajanowski, M. Borggrefe, B. Brinkmann, I. Warnecke, H. Funke, Z.A. Bhuiyan, A.A. Wilde, G. Breithardt, and W. Haverkamp, De novo mutation in the SCN5A gene associated with early onset of sudden infant death. Circulation,2001.104(10):1158-64.
[124]Ruan, Y., N. Liu, R. Bloise, C. Napolitano, and S.G. Priori, Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients. Circulation,2007.116(10):1137-44.
[125]Albert, C.M., E.G. Nam, E.B. Rimm, H.W. Jin, R.J. Hajjar, D.J. Hunter, C.A. MacRae, and P.T. Ellinor, Cardiac sodium channel gene variants and sudden cardiac death in women. Circulation,2008.117(1):16-23.
[126]Clancy, C.E., M. Tateyama, H. Liu, X.H. Wehrens, and R.S. Kass, Non-equilibrium gating in cardiac Na+ channels:an original mechanism of arrhythmia. Circulation,2003.107(17):2233-7.
[127]Rivolta, I., H. Abriel, M. Tateyama, H. Liu, M. Memmi, P. Vardas, C. Napolitano, S.G Priori, and R.S. Kass, Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes. J Biol Chem,2001.276(33): 30623-30.
[128]Dun, W. and P.A. Boyden, The Purkinje cell; 2008 style. J Mol Cell Cardiol, 2008.45(5):617-24.
[129]Haissaguerre, M., F. Extramiana, M. Hocini, B. Cauchemez, P. Jais, J.A. Cabrera, J. Farre, A. Leenhardt, P. Sanders, C. Scavee, L.F. Hsu, R. Weerasooriya, D.C. Shah, R. Frank, P. Maury, M. Delay, S. Garrigue, and J. Clementy, Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes. Circulation,2003.108(8):925-8.
[130]Yan, GX., Y. Wu, T. Liu, J. Wang, R.A. Marinchak, and P.R. Kowey, Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome:direct evidence from intracellular recordings in the intact left ventricular wall. Circulation,2001.103(23):2851-6.
[131]Benhorin, J., R. Taub, M. Goldmit, B. Kerem, R.S. Kass, I. Windman, and A. Medina, Effects of flecainide in patients with new SCN5A mutation: mutation-specific therapy for long-QT syndrome? Circulation,2000.101(14): 1698-706.
[132]Moss, A.J., W. Zareba, K.Q. Schwarz, S. Rosero, S. McNitt, and J.L. Robinson, Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. J Cardiovasc Electrophysiol,2008. 19(12):1289-93.
[133]Schwartz, P.J., S.G Priori, E.H. Locati, C. Napolitano, F. Cantu, J.A. Towbin, M.T. Keating, H. Hammoude, A.M. Brown, and L.S. Chen, Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+channel blockade and to increases in heart rate. Implications for gene-specific therapy. Circulation,1995.92(12):3381-6.
[134]Bankston, J.R. and R.S. Kass, Molecular determinants of local anesthetic action of beta-blocking drugs:Implications for therapeutic management of long QT syndrome variant 3. J Mol Cell Cardiol,2009.48(1):246-53.
[135]Fabritz, L., P. Kirchhof, M.R. Franz, D. Nuyens, T. Rossenbacker, A. Ottenhof, W. Haverkamp, G. Breithardt, E. Carmeliet, and P. Carmeliet, Effect of pacing and mexiletine on dispersion of repolarisation and arrhythmias in DeltaKPQ SCN5A(long QT3) mice. Cardiovasc Res,2003.57(4):1085-93.
[136]Schwartz, P.J., S.G Priori, M. Cerrone, C. Spazzolini, A. Odero, C. Napolitano, R. Bloise, GM. De Ferrari, C. Klersy, A.J. Moss, W. Zareba, J.L. Robinson, W.J. Hall, P.A. Brink, L. Toivonen, A.E. Epstein, C. Li, and D. Hu, Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome. Circulation,2004.109(15):1826-33.
[137]Benson, D.W., D.W. Wang, M. Dyment, T.K. Knilans, F.A. Fish, M.J. Strieper, T.H. Rhodes, and A.L. George, Jr., Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest,2003.112(7):1019-28.
[138]Lei, M., C.L. Huang, and Y. Zhang, Genetic Na+ channelopathies and sinus node dysfunction. Prog Biophys Mol Biol,2008.98(2-3):171-8.
[139]Makiyama, T., M. Akao, K. Tsuji, T. Doi, S. Ohno, K. Takenaka, A. Kobori, T. Ninomiya, H. Yoshida, M. Takano, N. Makita, F. Yanagisawa, Y. Higashi, Y. Takeyama, T. Kita, and M. Horie, High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations. J Am Coll Cardiol,2005.46(11):2100-6.
[140]Probst, V., F. Kyndt, F. Potet, J.N. Trochu, G. Mialet, S. Demolombe, J.J. Schott, I. Baro, D. Escande, and H. Le Marec, Haploinsufficiency in combination with aging causes SCN5A-linked hereditary Lenegre disease. J Am Coll Cardiol,2003.41(4):643-52.
[141]Schott, J.J., C. Alshinawi, F. Kyndt, V. Probst, T.M. Hoorntje, M. Hulsbeek, A.A. Wilde, D. Escande, M.M. Mannens, and H. Le Marec, Cardiac conduction defects associate with mutations in SCN5A. Nat Genet,1999. 23(1):20-1.
[142]Tan, H.L., M.T. Bink-Boelkens, C.R. Bezzina, P.C. Viswanathan, GC. Beaufort-Krol, P.J. van Tintelen, M.P. van den Berg, A.A. Wilde, and J.R. Balser, A sodium-channel mutation causes isolated cardiac conduction disease. Nature,2001.409(6823):1043-7.
[143]Makita, N., Phenotypic overlap of cardiac sodium channelopathies: individual-specific or mutation-specific? Circ J,2009.73(5):810-7.
[144]Veldkamp, M.W., R. Wilders, A. Baartscheer, J.G Zegers, C.R. Bezzina, and A.A. Wilde, Contribution of sodium channel mutations to bradycardia and sinus node dysfunction in LQT3 families. Circ Res,2003.92(9):976-83.
[145]Grant, A.O., M.P. Carboni, V. Neplioueva, C.F. Starmer, M. Memmi, C. Napolitano, and S. Priori, Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation. J Clin Invest,2002.110(8):1201-9.
[146]Priori, S.G, C. Napolitano, P.J. Schwartz, R. Bloise, L. Crotti, and E. Ronchetti, The elusive link between LQT3 and Brugada syndrome:the role of flecainide challenge. Circulation,2000.102(9):945-7.
[147]Olson, T.M., V.V. Michels, J.D. Ballew, S.P. Reyna, M.L. Karst, K.J. Herron, S.C. Horton, R.J. Rodeheffer, and J.L. Anderson, Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA,2005.293(4): 447-54.
[148]Chen, L.Y., J.D. Ballew, K.J. Herron, R.J. Rodeheffer, and T.M. Olson, A common polymorphism in SCN5A is associated with lone atrial fibrillation. Clin Pharmacol Ther,2007.81(1):35-41.
[149]Ellinor, P.T., E.G. Nam, M.A. Shea, D.J. Milan, J.N. Ruskin, and C.A. MacRae, Cardiac sodium channel mutation in atrial fibrillation. Heart Rhythm,2008. 5(1):99-105.
[150]Kusano, K.F., M. Taniyama, K. Nakamura, D. Miura, K. Banba, S. Nagase, H. Morita, N. Nishii, A. Watanabe, T. Tada, M. Murakami, K. Miyaji, S. Hiramatsu, K. Nakagawa, M. Tanaka, A. Miura, H. Kimura, S. Fuke, W. Sumita, S. Sakuragi, S. Urakawa, J. Iwasaki, and T. Ohe, Atrial fibrillation in patients with Brugada syndrome relationships of gene mutation., electrophysiology, and clinical backgrounds. J Am Coll Cardiol,2008.51(12): 1169-75.
[151]Li, Q., H. Huang, G. Liu, K. Lam, J. Rutberg, M.S. Green, D.H. Birnie, R. Lemery, M. Chahine, and M.H. Gollob, Gain-of-function mutation of Navl.5 in atrial fibrillation enhances cellular excitability and lowers the threshold for action potential firing. Biochem Biophys Res Commun,2009.380(1):132-7.
[152]Makiyama, T., M. Akao, S. Shizuta, T. Doi, K. Nishiyama, Y. Oka, S. Ohno, Y. Nishio, K. Tsuji, H. Itoh, T. Kimura, T. Kita, and M. Horie, A novel SCN5A gain-of-function mutation M1875T associated with familial atrial fibrillation. J Am Coll Cardiol,2008.52(16):1326-34.
[153]Benito, B., R. Brugada, R.M. Perich, E. Lizotte, J. Cinca, L. Mont, A. Berruezo, J.M. Tolosana, X. Freixa, P. Brugada, and J. Brugada, A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation. Heart Rhythm,2008.5(10):1434-40.
[154]Schwartz, P.J., M. Stramba-Badiale, A. Segantini, P. Austoni, G. Bosi, R. Giorgetti, F. Grancini, E.D. Marni, F. Perticone, D. Rosti, and P. Salice, Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med,1998.338(24):1709-14.
[155]Schwartz, P.J., S.G. Priori, R. Dumaine, C. Napolitano, C. Antzelevitch, M. Stramba-Badiale, T.A. Richard, M.R. Berti, and R. Bloise, A molecular link between the sudden infant death syndrome and the long-QT syndrome. N Engl J Med,2000.343(4):262-7.
[156]Arnestad, M., L. Crotti, T.O. Rognum, R. Insolia, M. Pedrazzini, C. Ferrandi, A. Vege, D.W. Wang, T.E. Rhodes, A.L. George, Jr., and P.J. Schwartz, Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation,2007.115(3):361-7.
[157]Wang, D.W., R.R. Desai, L. Crotti, M. Arnestad, R. Insolia, M. Pedrazzini, C. Ferrandi, A. Vege, T. Rognum, P.J. Schwartz, and A.L. George, Jr., Cardiac sodium channel dysfunction in sudden infant death syndrome. Circulation, 2007.115(3):368-76.
[158]Otagiri, T., K. Kijima, M. Osawa, K. Ishii, N. Makita, R. Matoba, K. Umetsu, and K. Hayasaka, Cardiac ion channel gene mutations in sudden infant death syndrome. Pediatr Res,2008.64(5):482-7.
[159]Probst, V., I. Denjoy, P.G Meregalli, J.C. Amirault, F. Sacher, J. Mansourati, D. Babuty, E. Villain, J. Victor, J.J. Schott, J.M. Lupoglazoff, P. Mabo, C. Veltmann, L. Jesel, P. Chevalier, S.A. Clur, M. Haissaguerre, C. Wolpert, H. Le Marec, and A.A. Wilde, Clinical aspects and prognosis of Brugada syndrome in children. Circulation,2007.115(15):2042-8.
[160]McNair, W.P., L. Ku, M.R. Taylor, P.R. Fain, D. Dao, E. Wolfel, and L. Mestroni, SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation,2004.110(15):2163-7.
[161]Ge, J., A. Sun, V. Paajanen, S. Wang, C. Su, Z. Yang, Y. Li, J. Jia, K. Wang, Y. Zou, L. Gao, and Z. Fan, Molecular and clinical characterization of a novel SCN5A mutation associated with atrioventricular block and dilated cardiomyopathy. Circ Arrhythm Electrophysiol,2008.1(2):83-92.
[162]Nguyen, T.P., D.W. Wang, T.H. Rhodes, and A.L. George, Jr., Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia. Circ Res,2008.102(3):364-71.
[163]Hesse, M., C.S. Kondo, R.B. Clark, L. Su, F.L. Allen, C.T. Geary-Joo, S. Kunnathu, D.L. Severson, A. Nygren, W.R. Giles, and J.C. Cross, Dilated cardiomyopathy is associated with reduced expression of the cardiac sodium channel Scn5a. Cardiovasc Res,2007.75(3):498-509.
[164]Ueda, K., C. Valdivia, A. Medeiros-Domingo, D.J. Tester, M. Vatta, G. Farrugia, M.J. Ackerman, and J.C. Makielski, Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc Natl Acad Sci U S A,2008.105(27):9355-60.
[165]Watanabe, H., D. Darbar, D.W. Kaiser, K. Jiramongkolchai, S. Chopra, B.S. Donahue, P.J. Kannankeril, and D.M. Roden, Mutations in sodium channel betal- and beta2-subunits associated with atrial fibrillation. Circ Arrhythm Electrophysiol,2009.2(3):268-75.
[166]Wang, P., Q. Yang, X. Wu, Y. Yang, L. Shi, C. Wang, G. Wu, Y. Xia, B. Yang, R. Zhang, C. Xu, X. Cheng, S. Li, Y. Zhao, F. Fu, Y. Liao, F. Fang, Q. Chen, X. Tu, and Q.K. Wang, Functional dominant-negative mutation of sodium channel subunit gene SCN3B associated with atrial fibrillation in a Chinese GeneID population. Biochem Biophys Res Commun.398(1):98-104.