摘要
耳聋在耳鼻咽喉头颈外科常见病。由于滥用抗生素、噪声的污染、人口老龄化及高危遗传的婚姻等诸多因素,我国难治性感音神经性耳聋发病率正逐年增加。耳聋已成为我国第一致残疾病。因此防治耳聋,已成为临床上迫切需要解决的顽症之一。
Src家族是一种非受体型蛋白酪氨酸激酶,它通过催化底物酪氨酸残端的磷酸化反应,将ATP的磷酸基团转移到底物,从而改变底物的构象及活性。Src家族共有9个成员,广泛分布于全身各组织和细胞中。Src家族成员都有相似的结构,如共有6个功能结构域,其中C-末端的酪氨酸Tyr527和激酶区活化环的Tyr416在调节Src家族酶活性过程中起着关键的作用。已知在中枢神经系统,Src家族参与调节神经系统发育、迁徙、突触可塑性等生理过程,并介导缺血性损伤等兴奋毒性作用,如Src家族可通过磷酸化与细胞迁徙相关的蛋白,调控神经元在发育过程中的迁徙过程；Src家族成员Src可通过调控兴奋性受体NMDA受体磷酸化水平,促进长时程增强或长时程抑制的产生,调节突触可塑性,这被认为与癫痫、阿茨海默氏病等神经系统疾病的发病机制有关。有研究发现抑制蛋白酪氨酸激酶Src家族可有效缓解噪声引起的的耳蜗损害。因此,Src家族可能参与耳聋的病理生理过程。
听觉信息在耳蜗转换为听神经动作电位,传向中枢。听神经动作电位发放异常,可导致听力下降。动作电位的产生主要取决于电压门控性钠通道和钾通道的开放。目前已明确调控听神经元电压门控性离子通道磷酸化水平,可影响听神经动作电位发放。研究虽已证实Src家族可参与调控电压门控性钠通道和钾通道,但对于Src家族在神经系统直接调控钠通道和钾通道的机制,目前并不明确；尤其是在听觉神经系统的研究,尚处于空白。耳蜗螺旋神经节神经元(SGN)是初级听觉神经元,是连接外周毛细胞和听觉中枢的重要枢纽,听神经动作电位起于SGN。已知SGN常是噪声和耳毒性药物等兴奋毒性作用的靶点。SGN的电压门控性钠通道和钾通道开放异常可影响听力。因此在本实验中,通过细胞原代培养技术,建立SGN体外培养模型；利用全细胞记录膜片钳技术,观察内源性Src家族被抑制后对SGN电压门控性钠通道和钾通道的作用特点,明确Src家族是否参与调控听神经系统动作电位的传导。通过观察Src家族各种调节因子对SGN电压门控性钠通道和钾通道的I-V曲线,钠电流宏观激活和失活(macroscopic activation and inactivation),电导,激活曲线,稳态失活曲线和失活后恢复曲线等电生理学特性的作用,明确Src家族在调控听神经动作电位过程的作用机制。最后观察Src家族代表性成员Src对SGN钠通道和钾通道的作用。通过本实验,将有利于揭示Src家族在听神经动作电位传播过程所扮演的角色,也为临床上耳聋防治提供新的理论指导。
实验内容包括以下三部分：
第一部分：Src家族对螺旋神经节神经元电压门控性钠通道和钾通道的调控研究目的：观察蛋白酪氨酸激酶Src家族对原代培养的大鼠螺旋神经节神经元(SGN)电压门控性钠通道和钾通道电生理学性质的作用,探讨Src家族对SGN听神经动作电位产生过程的影响。
研究方法：将SGN从耳蜗中分离出并原代培养,.24h后结合免疫荧光染色技术,首先利用抗N-200抗体和Hoechst3342鉴定SGN,然后用抗Src家族抗体,明确Src家族在SGN的表达。采用全细胞记录膜片钳技术,证实去极化刺激引出的内向和外向电流分别为电压门控性钠通道电流和电压门控性钾通道电流。Src家族被抑制后,观察同时记录的SGN电压门控性钠通道和钾通道电流的变化,明确Src家族对钠通道和钾通道的作用特点。再用无钠(NMDG)细胞外液置换正常NaCl细胞外液,观察Src家族被抑制后,对SGN电压门控性钾电流和1-V曲线的影响,明确Src家族对SGN钾通道作用。
结果：
(1)抗N-200抗体特异标记SGN胞膜,Hoechst3342可特异标记SGN胞核,证实从耳蜗分离出来的细胞为SGN。利用抗Src家族抗体,证实Src家族在SGN表达。
(2)TTX和CsCl可分别阻断由去极化刺激引出的内向电流和外向电流,证实内向电流为电压门控性钠通道电流(工Na),外向电流为电压门控性钾通道电流(IK)。
(3)10μM PP2作用后,抑制SGN的INa,INa为作用前59.6±15.7%(n=9, P <0.05);2μM SU6656作用后也抑制INa,INa为作用前68.6±7.5%(n=5,P<0.05)。而对照物10μM PP3和对照溶液作用后不影响SGN的INa。
(4) PP, PP3, SU6656以及对照溶液均不影响同时记录的IK。
(5)在NMDG细胞外液条件下,PP2, SU6656及对照溶液不影响钾通道I-V曲线的反转电位,也不影响IK。
结论：Src家族抑制后可抑制SGN电压门控性钠通道电流,但对电压门控性钾通道作用不明显。
第二部分：Src家族对螺旋神经节神经元电压门控性钠通道的调控及其电生理学机制
研究目的：观察Src家族在抑制和激活条件下,对SGN电压门控性钠通道电生理学特性的影响,明确Src家族调控钠通道机制。
研究方法：通过近距离给药方式,观察Src家族抑制剂PP2和SU6656,以及PP2拟合物PP3对SGN电压门控性钠通道电流(INa),I-V曲线,钠电流宏观激活和失活,电导,激活曲线,稳态失活曲线和失活后恢复曲线的作用。Src家族激活剂EPQ(pY)EEIPIA及其对照物则通过细胞内给药途径,同样观察Src家族激活后,SGN钠通道电流,I-V曲线及动力学性质的变化。
结果：
(1)10μMPP2作用后抑制SGN的INa,INa为给药前59.7±10%(n=7, P＜0.05)。2μM SU6656作用后也抑制INa,INa为给药前62±8.8%(n=7,P<0.05)。而1011M PP3和对照溶液不影响INa。
(2)PP2和SU6656不影响SGN INa的宏观激活和失活。
(3)PP2和SU6656作用后均抑制钠通道的I-V曲线峰值,但不影响1-V曲线钠通道反转电位。而PP3不影响I-V曲线。
(4)PP2作用前后,SGN钠通道的电导值分别为(6.7±1)nS和(5.2±0.7)nS(n=7,P<0.05)；而SU6656作用前后,SGN钠通道的电导值(11±2.4)nS和(7.9±1.9)nS(n=7,P<0.05)。PP2和SU6656均抑制SGN钠通道的电导。PP3不影响对SGN INa的电导。
(5)PP2和PP3, SU6656均不影响钠通道激活曲线。
(6)PP2作用前后,钠通道的半失活电压(V1/2)分别为(-69.4±0.8)mV和(-77.2±0.5)mV,斜率κ分别为(9.5±0.4)和(9.6±0.4)(n=11,P<0.05),PP2使钠通道的稳态失活曲线移向超极化方向。SU6656作用前后,V1/2分别为(-64.6±0.3)mV和(-70.1±0.4)mV,κ分别为(7.1±0.3)和(7.7±0.4)(n=9,P<0.05),SU6656也使钠通道的稳态失活曲线移向超极化方向。PP3不影响INa的稳态失活曲线。
(7)PP2作用前后,钠通道失活后恢复过程的时间常数分别为(7.8±4.5)ms和(17.4±5.9)ms(n=6,P<0.05),SU6656作用前后,钠通道失活后恢复过程的时间常数分别为(5±2.8)ms和(11.2±2.2)ms(n=6,P<0.05)。PP2和SU6656均延缓失活恢复过程。PP3不影响钠通道失活后恢复过程。
(8) EPQ(pY)EEIPIA(1mM)作用后增强INa，INa为作用前131.3±5.2%(n=12,P<0.05)。对照物EPQYEEIPIA(1mM)和空白对照不影响INa。
(9) EPQ(pY)EEIPIA不影响SGN INa的宏观激活和失活。
(10) EPQ(pY)EEIPIA作用后增强钠通道的I-V曲线峰值。EPQ(pY)EEIPIA和EPQYEEIPIA均不影响钠通道的I-V曲线反转电位。
(11)EPQ(pY)EEIPIA作用后增强SGN钠通道的电导,作用前后钠通道的电导值分别为(8.2±1.3)nS和(9.7±1.4)nS(n=9, P＜0.05)。EPQYEEIPIA不影响SGN钠通道的电导。
(12) EPQ(pY)EEIPIA作用前后,钠通道半激活电压(V1/2)分别为(-36.4±0.3)mV和(-40.2±0.4)mV,斜率K为(3.5±0.3)和(3.4±0.4)(n=9,P<0.05),钠通道的激活曲线移向超极化方向。EPQYEEIPIA不影响钠通道的激活曲线。
(13) EPQ(pY)EEIPIA和EPQYEEIPIA均不影响钠通道的稳态失活曲线。
(14) EPQ(pY)EEIPIA作用前后,SGN钠通道的失活后恢复时间常数分别为(5.6±2.5)ms和(6.1±2.8)ms(n=10, P＞0.05)。EPQ(pY)EEIPIA不影响钠通道的失活后恢复过程。
结论：Src家族的激活可上调SGN电压门控性钠通道的功能。Src家族不仅影响钠通道的电导,而且同时作用于钠通道的激活区和失活区,影响其激活过程和失活过程。Src家族对钠通道激活过程和失活过程的影响,与其活性水平有关。
第三部分Src家族成员Src对螺旋神经节神经元电压门控性钠通道的作用
研究目的：观察Src对SGN电压门控性钠通道电生理特性的影响,明确Src家族单个成员在调节SGN电压门控性钠通道过程中所起的作用。
研究方法：利用全细胞记录膜片钳技术,通过细胞内给药途径,观察Src特异抑制剂Src40-58对SGN INa,钠电流宏观激活和失活,I-V曲线,电导,激活曲线,稳态失活曲线以及失活后恢复曲线的作用。并观察PP2预处理后,Src40-58对SGN INa作用的变化。
结果：
(1) Src40-58(0.3mg/ml)抑制SGN INa,INa为给药前73.8±3.5%(n=10,P<0.05)。Src40-58还抑制I-V曲线峰值,但不影响反转电位。
(2)Src40-58不影响SGN INa的宏观激活和失活。
(3)Src40-58抑制SGN钠通道的电导,作用前后钠通道的电导分别为(12±2.5)nS和(10±3)nS(n=7,P<0.05)。
(4)Src40-58作用前后,钠通道半激活电压(V1/2)分别为(-38.5±0.4)mV和(-44.3±0.6)mV,斜率K为(3.8±0.4)和(3.2±0.5)(n=7,P<0.05)；而钠通道半失活电压(V1/2)分别为(-63.4±0.4)mV和(-67.9±0.5)mV,斜率K为(6.54±0.4)和(7.36±0.4)(n=9,P<0.05),钠通道的激活曲线和失活曲线均移向超极化方向。
(5)Src40-58影响SGN钠通道的失活后恢复曲线。Src40-58作用前后,钠通道的失活后恢复时间常数分别为(1.1±0.5)和(1.7±0.7)ms(n=6, P<0.05), Src40-58延缓SGN钠通道的失活后恢复过程。
(6)10μM PP2预处理5min,然后给予Src40-58,SGN INa为给药前96.5±11.7%(n=10,P>0.05),此时Src40-58不影响INa的大小,也不影响I-V曲线峰值和反转电位。
(7)PP2预处理后可阻断Src40-58对SGN钠通道的电导的抑制作用,作用前后钠通道的电导分别为(8±0.9)nS和(7.5±1.2)nS(n=7,P>0.05)。
(8)同理,PP2预处理后,Src40-58作用前后SGN钠通道的半失活电压(V1/2)分别为(-71.2±0.4)mV和(-73.3±0.4)mV,斜率K为(6.7±0.4)和(7.1±0.3)(n=8,P>0.05),稳态失活曲线未出现明显位移。而半激活电压(V1/2)分别为(-33.8±0.5)mV和(-39.9±1)mV,斜率K为(3.7±0.7)和(4.8±0.8)(n=9,P<0.05),钠通道的激活曲线仍移向超极化方向。
(9)同理,PP2预处理后阻断Src40-58对SGN钠通道的失活后恢复曲线的影响。Src40-58作用前后,钠通道的失活后恢复时间常数分别为(7±4.6)和(7.4±4.6)ms(n=6,P>0.05)。
结论：Src对SGN钠通道的具有与Src家族类似的抑制作用,主要通过抑制电导大小,增强其电压依赖性稳态失活过程,延缓失活后恢复过程。
Hearing loss is common in Otolaryngology. It is about10%of population suffer from different degrees of dearness in developed countries. The incidence of deafness in china is increasing also year by year because of these factors such as the abuse of antibiotics, noise pollution, population aging and genetic risk factors such as marriage. The prevention of hearing loss has become to be urgent to address in clinic. It is shown that the inhibition of tyrosine protein kinase, Src family kinase (SFKs), could prevent the cochlear damage from noise induced hearing loss. It is implied Src family may be involved in the pathological procedure of hearing loss.
SFKs is a family of non-receptor kinase that includes nine members. SFKs is able to catalyse the transfer of phosphate from ATP to a tyrosine residue of specific cell protein targets, and modify the molecular structure and activity of substrate. The activity of SFKs is regulated by the phophosrylation of tyrosine527in C terminus and tyrosine416in activation loop of kinase domain. It is invoved in the regulation of neurons development, migration, survival and synaptic plasticity, and also mediated the excitotoxicity process in nervous system, which may be the pathological mechanism of epilepsy, pain, Alzheimer's disease and others neurodegenerative disease.
Auditory information is converted as action potential in cochlear and then transmitted to the auditory central. Abnormal firing of auditory neurons can be lead to hearing loss. It is well known the voltage-gated sodium channel and potassium channels play critical roles in generation of action potentials. Some studies have indicated that the phosphorylated voltage-gated ion channels in auditory neurons would influence the firing of action potential. In addition, the voltage gated sodium and potassium channels are able to be regulated by SFKs in vivo. However, it is still unclear the effect of SFKs on sodium and potassium channels expressed in neurons, especially in auditory neurons. The cochlear spiral ganglion neurons (SGN) are primary auditory neurons, which interact with hair cells in peripheral and with auditory center in central. SGN is the origin of auditory action potential. Usually SGN is the target of excitotoxicity of noise or some ototoxic drugs. Dysfunction of voltage-gated sodium channels and potassium channels has proved to be induced hearing loss. Therefore, SGN cultured model in vivo was well established first by combination of cell primary culture technique and immunofluorescence staining in this study. The effect of endogenous SFKs on SGN voltage-gated sodium channel and potassium channel currents was investigated by whole cell configuration patch clamp technique. We also tested the regulation of I-V curve, activation curve and steady state inactivation curve of sodium channels and potassium channels by SFKs activator and inhibitor. To identify the role of Src in modification of action potential generated in SGN, we detected the influence of Src specific inhibitor Src40-58on the currents, macroscopic activation and inactivation, I-V curve, conductance, activation curve, steady state inactivation curve, recovery of INa on sodium and potassium channels. It will help us to illustrate the mechanism of cochlear impaired mediated by Src family, and provide a new guideline about deafness theorapy. This study is included three chapters:
Chapter1:The regulation of voltage-gated sodium and potassium channels in spiral ganglion neurons by endogenous Src family kinase
Objective:To understand the mechanism of regulation of action potential generation by SFKs, the effect of voltage-gated sodium and potassium channels in spiral ganglion neurons (SGN) by SFKs inhibitors was detected.
Methods:SGNs were dissected from cochlear tissue and plated into culture dishes. SGNs were identified by immunofluorescence staining. The location of SFKs in SGN was detected also. Inward and outward currents were indentified by TTX and Cs". To testify the effect on sodium channes and potassium channels in SGN by SFKs, the voltage-gated sodium and potassium channels currents were tested by whole cell configuration patch clamp technique after applied PP2, PP3, SU6656and vehicle. Subsequently, Na+in the extracellular solution was replaced with N-methy-D-Glucomine (NMDG) to block Na+currents. To investigate the regulation of Src kinase on voltage-gated potassium channel, potassium currents and Ⅰ-Ⅴ curve were detected when SFKs was applied.
Results:
(1) N-200selectively interacted with the membrane of SGN, and Hoechst3342selectively interacted with the nucleus of SGN. SFKs were detected in SGN by anti-SFKs antibody.
(2) TTX and Cs+could block the inward currents and outward currents induced by depolarized pulse.
(3) The sodium currents were significantly inhibited after applied10μM PP2or2μM SU6656. The currents is59.6±15.7%(n=9, P<0.05) and68.6±7.5%(n=5, P ＜0.05) compared with those recorded before SFKs inhibitors application. No significant change in the currents was found following application of PP3(10μM) or vehicle.
(4) No change in potassium currents recorded at the same time was induced following application of PP2, PP3, SU6656or vehicle.
(5) Potassium currents were recorded with Na+free extracellular solution in which Na+was replaced with NMDG. No change in potassium currents and I-V curve was detected following application of PP2, SU6656or vehicle.
Conclusions:The inhibition of SGN voltage-gated sodium channel is induced by SFKs inhibitors. There is no change on potassium currents after inhibited SFKs.
Chapter2:The regulation of kinetic of voltage-gated sodium channels in spiral ganglion neurons by endogenous Src family kinase
Objective:To investigate the mechanism of regulation on kinetic properties of voltage-gated sodium channels in SGN by SFKs.
Methods:K+in the solutions was replaced with Cs+to block potassium currents. PP2. PP3. SU6656were diluted into extracellular solution, and Src activated peptide EPQ(pY)EEIPIA and control peptide EPQYEEIPIA were diluted into intracellular solution. The sodium currents, macroscopic activation and inactivation. I-V curve, conductance, activation curve, steady state curve and recovery of inactivation were tested following applied SFKs inhibitors or activators.
Results:
(1) The sodium currents were significantly reduced when applied10μM PP2or2μM SU6656. The currents were59.7±10%(n=7, P＜0.05) and62±8.8%(n=7, P＜0.05) respectively, when compared with those recorded before SFKs inhibitors application. No significant change in the sodium currents was found following application of10μM PP3or vehicle.
(2) PP2and SU6656did not affect the macroscopic activation and inactivation.
(3) Application of PP2or SU6656significantly reduced peak Na+current density in I-V curve without changing reversal potential. PP3or vehicle application did not produce such changes.
(4) PP2reduced the conductance of sodium channel in SGN (control:6.7±1nS; PP2:5.2±0.7nS, n=7, P＜0.05). SU6656also reduced the conductance of sodium channel (control:11±2.4nS; SU6656:7.9±1.9nS, n=7, P＜0.05). PP3did not change the the conductance of sodium channel.
(5) No change in activation curve of sodium channel was induced following application of PP2, PP3and SU6656.
(6) The steady state inactivation curve was shifted to the left after PP2application (control:V1/2=-69.4±0.8mV, k=9.5±0.4; PP2:V1/2=-77.2±0.5mV, k=9.6±0.4, n=11,P＜0.05). Similarly, the steady state inactivation curve was also shifted to the left after application of SU6656(control:V1/2=-64.6±0.3mV, k=7.1±0.3; SU6656:V1/2=-70.1±0.4mV, k=7.7±0.4, n=9, P＜0.05). No significant change in the steady state inactivation curve was found following application of PP3.
(7) The time constant of recovery of sodium channel was reduced by PP2(control:7.8±4.5ms; PP2:17.4±5.9ms; n=6, P＜0.05). The time constant of recovery of sodium channel was also reduced by SU6656(control:5±2.8ms; SU6656:11.2=2.2ms, n=6, P＜0.05). PP3did not affect the time constant of recovery.
(8) The sodium currents were significantly potentiated when applied EPQ(pY)EEIPIA (1mM). The currents is131.3±5.2%(n=12, P＜0.05) comparing with the currents recorded immediately after the breakthrough. No significant change in the sodium currents was found following application of EPQYEEIPIA (1mM) or control pipette solution.
(9) EPQ(pY)EEIPIA did not influence the macroscopic activation and inactivation.
(10) Application of EPQ(pY)EEIPIA significantly increased peak Na+current density in I-V curve. EPQ(pY)EEIPIA did not change reversal potential. EPQYEEIPIA did not produce such changes.
(11) EPQ(pY)EEIPIA inceased the conductance of sodium channel in SGN (control:8.2±1.3nS; EPQ(pY)EEIPIA:9.7±1.4nS, n=9, P＜0.05). EPQYEEIPIA did not produce such changes.
(12) The activation curve was shifted to the left after EPQ(pY)EEIPIA application (control:V1/2:-36.4±0.3mV, k=3.5±0.3; EPQ(pY)EEIPIA:V1/2=-40.2±0.4mV, k=3.4±0.4, n=7, P＜0.05). No significant change in the activation curve was found following application of EPQYEEIPIA.
(13) No change in activation curve of sodium channel was induced following application of either EPQ(pY)EEIPIA or EPQYEEIPIA.
(14) The time constant of recovery of sodium channel was reduced by EPQ(pY)EEIPIA (control:5.6±2.5ms; EPQ(pY)EEIPIA:6.1±2.8ms, n=10, P＞0.05). EPQYEEIPIA did not produce such changes.
Conclusions:Src family kinase regulates the voltage-gated sodium channels activtity in SGN. The conductance, activation and the steady-state inactivation of sodium channels are likely subjects to SFKs regulations. The effect on activation and inactivation of sodium channels is depended on the enzyme activity.
Chapter3:The effect of Src on voltage-gated sodium channels in spiral ganglion neurons
Objective:To testify the regulation on voltage-gated sodium channel in spiral ganglion neurons by Src.
Methods:Src40-58was diluted into intracellular solution. The sodium currents, macroscopic activation and inactivation, I-V curve, conductance, activation curve, steady state inactivation curve and recovery of INa were detected by whole cell configuration patch clamp technology. The effect of Src40-58on sodium currents in SGN was tested followed PP2pre-treated.
Results:
(1) The sodium currents were significantly reduced when applied Src40-58(0.3mg/ml). The currents were73.8±3.5%(n=10, P＜0.05) compared with those recorded before Src40-58application. Src40-58also reduced peak Na+current density in I-V curve without changing reversal potential.
(2) Src40-58did not affect the macroscopic activation and inactivation.
(3) Src40-58reduced the conductance of sodium channel in SGN (control:12±2.5nS:Src40-58:10±3nS. n=7. P＜0.05).
(4) The steady state inactivation curve was shifted to the left following application of Src40-58(control:V1/2=-63.4±0.4mV, k=6.5±0.4; Src40-58:V1/2=-67.9±0.5mV,k=7.4±0.4, n=9, P＜0.05). Moreover, the activation curve was shifted to the left following application of Src40-58(control:V1/2=-38.5±0.4mV, k=3.8±0.4; Src40-58:V1/2=-44.3±0.6mV,k=3.2±0.5, n=7, P＜0.05).
(5) The time constant of recovery of sodium channel was reduced by Src40-58(control:1.1±0.5ms; Src40-58:1.7±0.7ms, n=6, P＜0.05).
(6) The inhibiton of Src40-58on the amplitude of sodium channel in SGN could be prevented in SGN bathed with solution with PP2(96.5±11.7%, n=10, P＞0.05). In this case, No change on peak Na+current density in I-V curve in SGN was found either.
(7) The reduction on the conductance of sodium channel in SGN by Src40-58was prevented by PP2pre-treatment (control:8±0.9nS; Src40-58:7.5±1.2nS, n=7, P＞0.05).
(8) The shift on steady state inactivation curve induced by Src40-58in SGN was prevented following PP2pre-treatment (control:V1/2=-71.2±0.4mV, k=6.7±0.4; Src40-58:V1/2=-73.3±0.4mV, k=7.1±0.3, n=8, P＞0.05). However, following application of Src40-58, the activation curve was still shifted to the left in SGN when was pre-treated by PP2(control:W1/2=-33.8±0.5mV, k=3.7±0.7; Src40-58: V1/2=-39.9±1mV, k=4.8±0.8, n=9, P＜0.05).
(9) Following application of Src40-58, no change on the time constant of recovery of sodium channel was found in SGN bathed with PP2(control:7±4.6ms:Src40-58:7.4±4.6ms; n=6, P＞0.05).
Conclusions:Src is involved in the regulation of sodium channels in SGN. The effect of Src on sodium channels in SGN is similar as that of SFKs
引文
1. Martin,G.S. The hunting of the Src. Nat Rev Mol Cell Biol 2,467-475 (2001).
2. Jacobs C, Rubsamen H. Expression of pp60c-src protein kinase in adult and fetal human tissue:high activities in some sarcomas and mammary carcinomas. Cancer Research 43,1696-1702 (1983).
3. Bolen JB, Veillette A, Schwartz AM, etc. Activation of pp60c-src protein kinase activity in human colon carcinoma. Proc Natl Acad Sci U S A 84, 2251-2255(1987).
4. Irby RB, Mao W, Coppola D, etc. Activating SRC mutation in a subset of advanced human colon cancers. Nature Genetics 21,187-190 (1999).
5.李鑫,齐宇,张明智等。Src家族酪氨酸激酶Fyn在肺鳞状细胞癌组织中的表达及意义.肿瘤防治研究 7,50-53(2010).
6. Cooke MP, Perlmutter RM. Expression of a novel form of the fyn proto-oncogene in hematopoietic cells. New biologist 1,66-74 (1983).
7. Cotton,P.C., Brugge,J.S. Neural tissues express high levels of the cellular src gene product pp60c-src. Mol. Cell. Biol.3,1157-1162 (1983).
8. Sudol,M. Hanafusa,H. Cellular proteins homologous to the viral yes gene product. Mol. Cell. Biol.6,2839-2846 (1986).
9. Yu,X.M., Askalan,R., Keil,G.J. etc. NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science 275,674-678 (1997).
10. Hayashi,T. Huganir.R.L. Tyrosine Phosphorylation and Regulation of the AMPA Receptor by Src Family Tyrosine Kinases. The Journal of Neuroscience 24,6152-6160 (2004).
11.李勇,裴林,张光毅.脑缺血/再灌对蒙古沙土鼠海马突触体酪氨酸磷酸化的进展.生理学报 52,137-142(2000).
12. Hou XY, Zhang.G., Yan.JZ.etc Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn- PSD95-NR2A complex after transient brain ischemia. Brain Research 955, 123-132(2002).
13. Hou XY, Zhang.GY.Zong.YY. Suppression of postsynaptic density protein 95 expression attenuates increased tyrosine phosphorylation of NR2A subunits of N-methyl-D-aspartate receptors and interactions of Src and Fyn with NR2A after transient brain ischemia in rat hippocampus. Neuroscience Letters 343,125-128(2003).
14.孟凡军,张炳熙,纪方等.吗啡预处理对小鼠海马脑片氧-糖缺失/恢复时CaMK Ⅱ和NMDA受体的影响.中华麻醉学杂志 26,1008-1011(2006).
15. Chin J, Palop JJ, Puolivali J.etc Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease. Journal of Neuroscience 25,9694-9703 (2005).
16. Chin J, Palop JJ., Yu GQ.etc Fyn kinase modulates synaptotoxicity, but not aberrant sprouting, in human amyloid precursor protein transgenic mice. Journal of Neuroscience 24,4692-4697 (2004).
17. Jurd R, Tretter V, Walker J.etc Fyn kinase contributes to tyrosine phosphorylation of the GABA(A) receptor gamma2 subunit. Molecular and Cellular Neurosciences 44,129-134 (2010).
18. Gutman,G.A., Chandy KG, Adelman JP. etc. International Union of Pharmacology. XLI. Compendium of Voltage-Gated Ion Channels: Potassium Channels. Pharmacological Reviews 55,583-586 (2003).
19. Dai,S.P., Hall,D.D., Hell,J.W. Supramolecular Assemblies and Localized Regulation of Voltage-Gated Ion Channels. Physiological Reviews 89,411-452 (2009).
20. Beacham.D.. Ahn,M.. Catterall.W.A. etc. Sites and molecular mechanisms of modulation of Na(v)1.2 channels by fyn tyrosine kinase. Journal of Neuroscience 27,11543-11551 (2007).
21. Jia Z,,Jia.Y.Liu.B.etc. Genistein inhibits voltage-gated sodium currents in SCG neurons through protein tyrosine kinase-dependent and kinase-independent mechanisms. Pflugers Archiv European Journal of Physiology 456,857-866 (2008).
22. Gamper N, Stockand JD, Shapiro MS. Subunit-specific modulation of KCNQ potassium channels by Src tyrosine kinase. Journal of Neuroscience 23,84-95 (2003).
23. Mackenzie,F.E. Parker A, Parkinson NJ, etc. Analysis of the mouse mutant Cloth-ears shows a role for the voltage-gated sodium channel Scn8a in peripheral neural hearing loss. Genes, Brain and Behavior 8,699-713 (2009).
24. Karcz A,H. Hennig MH, Robbins CA.etc Low-voltage activated Kvl.1 subunits are crucial for the processing of sound source location in the lateral superior olive in mice. Journal of Physiology (2011).
25. Lin,X. Action potentials and underlying voltage-dependent currents studied in cultured spiral ganglion neurons of the postnatal gerbil. Hearing Research 108,157-179(1997).
26. Hossain WA, Antic SD, Yang Y.etc Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea. Journal of Neuroscience 25,6857-6868 (2005).
27. Lin,X., Chen,S.,Tee,D. Effects of Quinine on the Excitability and Voltage-Dependent Currents of Isolated Spiral Ganglion Neurons in Culture. Journal of Neurophysiology 79,2503-2512 (1998).
28. Macica CM, Kaczmarek LK. Casein kinase 2 determines the voltage dependence of the Kv3.1 channel in auditory neurons and transfected cells. Journal of Neuroscience 21,1160-1168 (2001).
29. Harris KC, Hu.B. Hangauer D.etc Prevention of noise-induced hearing loss with Src-PTK inhibitors. Hearing Research 208,14-25 (2005).
30.冯爽,苏纪平,唐小兰.水杨酸钠抑制大鼠螺旋神经节神经元电压门控性钠通道.广西医科大学学报 1,1-4(2010).
1. Mott JB, Norton SJ, etc. Neely ST Changes in spontaneous otoacoustic emissions produced by acoustic stimulation of the contralateral ear. Hearing Research 38,229-242 (1989).
2. Collet L, Kemp DT, Veuillet E, etc. Effect of contralateral auditory stimuli on active cochlear micro-mechanical properties in human subjects. Hearing Research 43,251-261 (1990).
3. Whitehead ML, Martin GK, Lonsbury-Martin BL. Effects of the crossed acoustic reflex on distortion-product otoacoustic emissions in awake rabbits. Hearing Research 51,55-72 (1991).
4.孙建军,刘铤.螺旋神经节神经元原代培养及其免疫细胞化学鉴定.中华耳鼻咽喉科杂志4,36-39(1998).
5. Santos-Sacchi J. Voltage-dependent ionic conductances of type I spiral ganglion cells from the guinea pig inner ear. The Journal of Neuroscience 13, 3599-3611 (1993).
6. Lin Xi. Action potentials and underlying voltage-dependent currents studied in cultured spiral ganglion neurons of the postnatal gerbil. Hearing Research 108,157-179(1997).
7. Yang B, Desai R, Kaczmarek LK. Slack and Slick K(Na) channels regulate the accuracy of timing of auditory neurons. Journal of Neuroscience 27, 2617-2627(2007).
8. Mo ZL. Adamson CL, Davis RL. Dendrotoxin-sensitive K+ currents contribute to accommodation in murine spiral ganglion neurons. Journal of Physiology 542,763-778 (2002).
9. Gui P, Wu X, Ling S. etc. Integrin Receptor Activation Triggers Converging Regulation of Cavl.2 Calcium Channels by c-Src and Protein Kinase A Pathways. Journal of Biological Chemistry 281,14015-14025 (2006).
10. Wu X, Davis GE, Meininger GA, etc. Regulation of the L-type Calcium Channel by 伪 β1 Integrin Requires Signaling between Focal Adhesion Proteins. Journal of Biological Chemistry 276,30285-30292 (2001).
11. Martin GS. The hunting of the Src. Nature Reviews Molecular Cell Biology 2,467-475(2001).
12. Stehelin D, Varmus HE, Bishop JM, etc. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260,170-173(1976).
13. Brugge JS, Erikson RL. Identification of transformation specific antigen induced by an avian sarcoma virus. Nature 269,346-348 (1977).
14. Collett MS, Brugge JS, Erikson RL. Characterization of a normal avian cell protein related to the avian sarcoma virus transforming gene product. Cell 15(4),1363-1369.12-1-1978.
15. Oppermann H, Levinson AD, Varmus HE, etc. Uninfected vertebrate cells contain a protein that is closely related to the product of the avian sarcoma virus transforming gene (src). Proc Natl Acad Sci U S A 76,1804-1808 (1979).
16. Kmiecik TE, Shalloway D. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation. Cell 49(1),65-73.4-10-1987.
17. Cartwright CA, Eckhart W, Simon S, etc. Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain. Cell 49(1),83-91.4-10-1987.
18. Piwnica-Worms H, Saunders KB, Roberts TM, etc. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell 49(1),75-82.4-10-1987.
19. Xu WQ. Doshi A. Lei M. Eck MJ. etc. Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Molecular Cell 3,629-638 (1999).
20. Nada S, Okada M, Macauley A, etc. Cloning of A Complementary-Dna for A Protein-Tyrosine Kinase That Specifically Phosphorylates A Negative Regulatory Site of P60C-Src. Nature 351,69-72 (1991).
21. Martin GS. The hunting of the Src. Nat Rev Mol Cell Biol 2,467-475 (2001).
22. Hanke JH, Gardner JP, Dow RL, etc. Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck-and FynT-dependent T cell activation. Journal of Biological Chemistry 271,695-701 (1996).
23. Liu Y, Bishop A, Witucki L, etc. Structural basis for selective inhibition of Src family kinases by PP1. Chemistry & Biology 6,671-678 (1999).
24. Blake RA, Broome MA, Liu X, etc. SU6656, a Selective Src Family Kinase Inhibitor, Used To Probe Growth Factor Signaling. Mol. Cell. Biol.20, 9018-9027(2000).
25. Hilborn MD, Vaillancourt RR, Rane SG. Growth factor receptor tyrosine kinases acutely regulate neuronal sodium channels through the Src signaling pathway. Journal of Neuroscience 18,590-600 (1998).
26. Beacham D, Ahn M, Catterall WA, etc. Sites and molecular mechanisms of modulation of Na(v)1.2 channels by Fyn tyrosine kin. Journal of Neuroscience 27,11543-11551 (2007).
27. Ahern CA, Zhang JF, Wookalis MJ, etc. Modulation of the cardiac sodium channel NaV1.5 by Fyn, a Src family tyrosine kinase. Circ Res 96,991-998 (2005).
28. Jia Z, Jia Y, Liu B, etc. Genistein inhibits voltage-gated sodium currents in SCG neurons through protein tyrosine kinase-dependent and kinase-independent mechanisms. Pflugers Archiv European Journal of Physiology 456,857-866 (2008).
29. Fryatt AG. Vial C. Mulheran M. etc. Voltage-gated sodium channel expression in rat spiral ganglion neurons. Molecular and Cellular Neurosciences 42,399-407 (2009).
30. George J. Dravid SM. Prakash A. etc. Sodium Channel Activation Augments NMDA Receptor Function and Promotes Neurite Outgrowth in Immature Cerebrocortical Neurons. The Journal of Neuroscience 29,3288-3301 (2009).
31. Rusznak Z, Szucs G. Spiral ganglion neurones an overview of morphology, firing behaviour, ionic channels and function. Pflugers Archiv European Journal of Physiology 4577,1303-1325 (2009).
32. Macica CM, Kaczmarek LK. Casein kinase 2 determines the voltage dependence of the Kv3.1 channel in auditory neurons and transfected cells. Journal of Neuroscience 21,1160-1168 (2001).
33. Kim SJ, Choi WS, Han JS, etc. A Novel Mechanism for the Suppression of a Voltage-gated Potassium Channel by Glucose-dependent Insulinotropic Polypeptide. Journal of Biological Chemistry 280,28692-28700 (2005).
34.刘先胜等蛋白激酶C对大鼠支气管平滑肌K v通道的影响.生理学报55,135-141(2003).
35. Hoshi N, Zhang JS, Omaki M, etc. AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists. Nat Neurosci 6,564-571 (2003).
36. Holmes TC, Fadool DA, Ren R, etc. Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain. Science 214,2089-2091 (1996).
37. Nitabach MN, Llamas DA, Araneda RC, etc. A mechanism for combinatorial regulation of electrical activity:Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors. Proc Natl Acad Sci U S A 98,705-710 (2001).
38. Gamper N, Stockand JD, Shapiro MS. Subunit-specific modulation of KCNQ potassium channels by Src tyrosine kinase. Journal of Neuroscience 23,84-95 (2003).
39. Fadool DA. Tyrosine phosphorylation downregulates a potassium current in rat olfactory bulb neurons and a cloned Kvl.3 channel. Annals of the New-York Academy of Sciences 855,529-532 (1998).
40. Strauss O, Rosenthal R, Dey D, etc. Effects of Protein Kinase C on Delayed Rectifier K+ Channel Regulation by Tyrosine Kinase in Rat Retinal Pigment Epithelial Cells. Investigative Ophthalmology & Visual Science 43,1645-1654 (2002).
1. Liu X, Brodeur SR, Gish G, etc. Regulation of c-Src tyrosine kinase activity by the Src SH2 domain. Oncogene 8,1119-1126 (1993).
2. Yu FH, Catterall WA. Overview of the voltage-gated sodium channel family. Genome Biology 4,207 (2003).
3. Catterall WA, Goldin AL, Waxman SG. International Union of Pharmacology. XLⅦ. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels. Pharmacological Reviews 57,397-409 (2005).
4. Scheuer T, Catterall WA. Control of neuronal excitability by phosphorylation and dephosphorylation of sodium channels. Biochemical Society transactions 34,1299-1302 (2006).
5. Lin Xi. Action potentials and underlying voltage-dependent currents studied in cultured spiral ganglion neurons of the postnatal gerbil. Hearing Research 108,157-179(1997).
6. Xin WK, Kwan CL, Zhao XH, etc. A Functional Interaction of Sodium and Calcium in the Regulation of NMDA Receptor Activity by Remote NMDA Receptors. The Journal of Neuroscience 25,139-148 (2005).
7. Xu J, Weerapura M, Ali MK, etc. Control of Excitatory Synaptic Transmission by C-terminal Src Kinase. Journal of Biological Chemistry 283,17503-17514(2008).
8. Chen Y, Yu FH, Surmeier DJ, etc. Neuromodulation of Na+ Channel Slow Inactivation via cAMP-Dependent Protein Kinase and Protein Kinase C. Neuron 49(3).409-420.2-2-2006.
9. Dai S. Hall DD. Hell JW. Supramolecular Assemblies and Localized Regulation of Voltage-Gated Ion Channels. Physiological Reviews 89,411-452 (2009).
10. Murphy BJ, Rossie S, De Jongh KS, etc. Identification of the sites of selective phosphorylation and dephosphorylation of the rat brain Na+ channel alpha subunit by cAMP-dependent protein kinase and phosphoprotein phosphatases. Journal of Biological Chemistry 268,27355-27362(1993).
11. Schreibmayer W, Frohnwieser B, Dascal N, etc. Beta-adrenergic modulation of currents produced by rat cardiac Na+ channels expressed in Xenopus laevis oocytes. Receptors Channels 2,339-350 (1994).
12. Frohnwieser B, Chen LQ, Schreibmayer W, etc. Modulation of the human cardiac sodium channel alpha-subunit by cAMP-dependent protein kinase and the responsible sequence domain. The Journal of Physiology 498,309-318(1997).
13. Frohnwieser B, Weigl L, Schreibmayer W. Modulation of cardiac sodium channel isoform by cyclic AMP dependent protein kinase does not depend on phosphorylation of serine 1504 in the cytosolic loop interconnecting transmembrane domains III and IV. Pflugers Archiv European Journal of Physiology 430,751-753 (1995).
14. Tibbs VC, Gray PC, Catterall WA, etc. AKAP15 Anchors eAMF-dependent Protein Kinase to Brain Sodium Channels. Journal of Biological Chemistry 273,25783-25788(1998).
15. Few WP, Scheuer T, Catterall WA. Dopamine modulation of neuronal Na+ channels requires binding of A kinase-anchoring protein 15and PKA by a modified leucine zipper motif. Proceedings of the National Academy of Sciences 104,5187-5192 (2007).
16. Numann R, Catterall WA, Scheuer T. Functional modulation of brain sodium channels by protein kinase C phosphorylation. Science 254,115-118 (1991).
17. Grueter CE, Abiria SA, Dzhura I, etc. L-Type Ca2+ Channel Facilitation Mediated by Phosphorylation of the?Subunit by CaMKII. Molecular cell 23(5).641-650.9-1-2006.
18. Jiang X, Lautermilch NJ, Watari H, etc. Modulation of CaV2.1 channels by Ca2+/calmodulin-dependent protein kinase Ⅱ bound to the C-terminal domain. Proceedings of the National Academy of Sciences 105.341-346 (2008).
19. Welsby PJ, Wang H, Wolfe JT, etc. A Mechanism for the Direct Regulation of T-Type Calcium Channels by Ca2+/Calmodulin-Dependent Kinase Ⅱ. The Journal of Neuroscience 23,10116-10121 (2003).
20. Yuill KH, Smirnov SV. Calcium-dependent regulation of voltage-gated sodium channels in cardiac myocytes:just the beginning? Cardiovascular Research 85,411-412 (2010).
21. Aiba T, Hesketh GG, Liu T, etc. Na+ channel regulation by Ca2+/calmodulin and Ca2+/calmodulin-dependent protein kinase Ⅱ in guinea-pig ventricular myocytes. Cardiovascular Research 85,454-463 (2010).
22.曹雪红,明章银,付晖等。蛋白丝/苏氨酸磷酸酶1和2A抑制药对大鼠三叉神经元电压依赖性那通道的影响.中国药理学与毒理学杂志19,253 (2005).
23. Hilborn MD, Vaillancourt RR, Rane SG. Growth factor receptor tyrosine kinases acutely regulate neuronal sodium channels through the src signaling pathway. Journal of Neuroscience 18,590-600 (1998).
24. Beacham D, Ahn M, Catterall WA, etc. Sites and molecular mechanisms of modulation of Na(v)1.2 channels by Fyn tyrosine kin. Journal of Neuroscience 27,11543-11551 (2007).
25. Ahern CA, Zhang JF, Wookalis MJ, etc. Modulation of the cardiac sodium channel NaV1.5 by Fyn, a Src family tyrosine kinase. Circ Res 96,991-998 (2005).
26. Jia Z, Jia Y, Liu B, etc. Genistein inhibits voltage-gated sodium currents in SCG neurons through protein tyrosine kinase-dependent and kinase-independent mechanisms. Pfliigers Archiv European Journal of Physiology 456,857-866 (2008).
27. Cantrell AR. Smith RD. Goldin AL. etc. Dopaminergic modulation of sodium current in hippocampal neurons via cAMP-dependent phosphorylation of specific sites in the sodium channel alpha subunit. Journal of Neuroscience 17.7330-7338 (1997).
28. Cantrell AR, Tibbs VC, Yu FH, etc. Molecular Mechanism of Convergent Regulation of Brain Na+ Channels by Protein Kinase C and Protein Kinase A Anchored to AKAP-15. Molecular and Cellular Neuroscience 21,63-80 (2002).
29. West JW, Numann R, Murphy BJ, etc. A phosphorylation site in the Na+ channel required for modulation by protein kinase C. Science 254,866-868 (1991).
30. Wang Y, Wagner MB, Kumar R, etc. Inhibition of fast sodium current in rabbit ventricular myocytes by protein tyrosine kinase inhibitors. Pflugers Archiv European Journal of Physiology 446,485-491 (2003).
31. Armstrong CM. Na channel inactivation from open and closed states. Proceedings of the National Academy of Sciences 103,17991-17996 (2006).
32. Sokolov S, Scheuer T, Catterall WA. Ion permeation through a voltage-sensitive gating pore in brain sodium channels having voltage sensor mutations. Neuron 47,183-189 (2005).
33. Marban E, Yamagishi T, Tomaselli GF. Structure and function of voltage-gated sodium channels. Journal of Physiology 508,647-657 (1998).
34. Bendahhou Sd, Cummins TR, Tawil R, etc. Activation and Inactivation of the Voltage-Gated Sodium Channel:Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation. The Journal of Neuroscience 19,4762-4771 (1999).
35. Kalia LV, Gingrich JR, Salter MW. Src in synaptic transmission and plasticity. Oncogene 23,8007-8016 (2004).
36. Gonfloni S, Williams JC, Hattula K, etc. The role of the linker between the SH2 domain and catalytic domain in the regulation and function of Src. EMBO J 16,7261-7271 (1997).
37. Cooper JA, Howell B. The when and how of Src regulation. Cell 73,1051-1054(1993).
38. Porter M. Schindler T. Kuriyan J, etc. Reciprocal Regulation of Hck Activity by Phosphorylation of Tyr527 and Tyr416. Journal of Biological Chemistry 275.2721-2726(2000).
39. Bradshaw JM. The Src, Syk. and Tec family kinases:Distinct types of molecular switches. Cellular Signalling 22,1175-1184 (2010).
1. Yu XM, Askalan R, Keil GJ, etc. NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science 275,674-678 (1997).
2. Fadool DA, Holmes TC, Berman K, etc. Tyrosine Phosphorylation Modulates Current Amplitude and Kinetics of a Neuronal Voltage-Gated Potassium Channel. Journal of Neurophysiology 78,1563-1573 (1997).
3. Kalia LV, Gingrich JR., Salter MW. Src in synaptic transmission and plasticity. Oncogene 23,8007-8016 (2004).
4. Yu XM, Salter MW. Gain control of NMDA-receptor currents by intracellular sodium. Nature 396,469-474 (1998).
5.邱彦.Src家族激酶的研究进展.中国药物应用与检测2,37-40(2004).
6. Brown MT, Cooper JA. Regulation, substrates and functions of src. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 1287,121-149 (1996).
7. Holmes TC, Fadool DA, Ren R, etc. Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain. Science 274,2089-2091 (1996).
8. Nitabach MN, Llamas DA, Araneda RC, etc. A mechanism for combinatorial regulation of electrical activity:Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors. Proc Natl Acad Sci U S A 98,705-710 (2001).
9. Takagi N, Cheung HH. Bissoon N, etc. The Effect of Transient Global Ischemia on the Interaction of Src and Fyn With the N-Methyl-D-Aspartate Receptor and Postsynaptic Densities [colon] Possible Involvement of Src Homology 2 Domains. J Cereb Blood Flow Metab 19,880-888 (1999).
10. Groveman BR, Xue S, Marin V, etc. Roles of the SH2 and SH3 domains in the regulation of neuronal Src kinase functions. FEBS Journal 278,643-653 (2011).
11. Yu XM, Salter MW. Src, a molecular switch governing gain control of synaptic transmission mediated by N-methyl-d-aspartate receptors. Proceedings of the National Academy of Sciences 96,7697-7704 (1999).
12. Gingrich JR., Pelkey KA, Fam SR, etc. Unique domain anchoring of Src to synaptic NMDA receptors via the mitochondrial protein NADH dehydrogenase subunit 2. Proceedings of the National Academy of Sciences of the United States of America 101,6237-6242 (2004).
13. Liu XJ, Gingrich JR., Vargas-Caballero M, etc. Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex. Nat Med 14,1325-1332 (2008).
14. Salter MW, Kalia LV. Src kinases:a hub for NMDA receptor regulation. Nature reviews. Neuroscience 5,317-328 (2004).
15. Beacham D, Ahn M, Catterall WA, etc. Sites and molecular mechanisms of modulation of Na(v)1.2 channels by Fyn tyrosine kin. Journal of Neuroscience 27,11543-11551 (2007).
16. Ahern CA, Zhang JF, Wookalis MJ, etc. Modulation of the cardiac sodium channel NaV1.5 by Fyn, a Src family tyrosine kinase. Circ Res 96,991-998 (2005).
17. Fryatt AG, Vial C, Mulheran M, etc. Voltage-gated sodium channel expression in rat spiral ganglion neurons. Molecular and Cellular Neurosciences 42,399-407 (2009).
18. Grant SG, O'Dell TJ, Karl KA, etc. Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice. Science 258, 1903-1910(1992).
19. Beggs HE, Soriano P, Maness PF. NCAM-dependent neurite outgrowth is inhibited in neurons from Fyn-minus mice. Journal of Cell Biology 127, 825-833 (1994).
1. Catterall,W.A., Goldin,A.L. Waxman,S.G. International Union of Pharmacology. XL VII. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels. Pharmacological Reviews 57,397-409 (2005).
2. Ferrera,L. Moran,O.β1-subunit modulates the Nav1.4 sodium channel by changing the surface charge. Experimental Brain Research 172,139-150 (2006).
3.于耀清,陈军.电压门控性钾、钠、钙离子通道的结构及分类.中华神经医学杂志4,520(2005).
4. Yu FH, Catterall WA. Overview of the voltage-gated sodium channel family. Genome Biology 4,207 (2003).
5. Goldin,A.L. Evolution of voltage-gated Na+ channels. J Exp Biol 205, 575-584 (2002).
6.任成涛；欧绍武；王运杰等大鼠脑组织N a v 1.5钠通道的基因克隆与分布分析.生物化学与生物物理进展34,816-823(2007).
7. Gutman GA, Chandy KG, Adelman JP. etc. International Union of Pharmacology. XLI. Compendium of Voltage-Gated Ion Channels: Potassium Channels. Pharmacological Reviews 55,583-586 (2003).
8. Dolphin,A.C. Subunits of Voltage-Gated Calcium Channels. Journal of Bioenergetics and Biomembranes 35.599-620 (2003).
9. Cuchillo-Ibanez,I. Aldea M, Brocard J etc. Inhibition of voltage-gated calcium channels by sequestration of [beta] subunits. Biochemical and Biophysical Research Communications 311,1000-1007 (2003).
10. Catterall,W.A., Striessnig.J., Snutch,T.P.etc. International Union of Pharmacology. XL. Compendium of Voltage-Gated Ion Channels: Calcium Channels. Pharmacological Reviews 55,579-581 (2003).
11. Catterall,W.A. STRUCTURE AND REGULATION OF VOLTAGE-GATED Ca2+ CHANNELS. Annu. Rev. Cell Dev. Biol.16,521-555 (2000).
12. Xu J, Weerapura M, Ali MK.etc. Control of Excitatory Synaptic Transmission by C-terminal Src Kinase. Journal of Biological Chemistry 283,17503-17514(2008).
13. Luo,J.H., Wang.Y.H., Yasuda,R.P.etc The majority of N-methyl-D-aspartate receptor complexes in adult rat cerebral cortex contain at least three different subunits (NR1/NR2A/NR2B). Molecular Pharmacology 51, 79-86(1997).
14. Hollmann,M., Maron.C., Heinemann,S. N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluRl. Neuron 13,1331-1343 (1994).
15. Sieghart,W. Unraveling the function of GABAA receptor subtypes. Trends in Pharmacological Sciences 21.411-413 (2000).
16. Olsen,R.W. Sieghart,W. GABAA receptors:Subtypes provide diversity of function and pharmacology. Neuropharmacology 56,141-148 (2009).
17. Brandon,N.J. Delmas P, Kittler JT. etc. GABAA Receptor Phosphorylation and Functional Modulation in Cortical Neurons by a Protein Kinase C-dependent Pathway. Journal of Biological Chemistry 275,38856-38862 (2000).
18. Houston?C.M., He,Q., Smart,T.G. CaMKII phosphorylation of the GABAA receptor:receptor subtype-and synapse-specific modulation. The Journal of Physiology 587.2115-2125 (2009).
19. Jurd,R., Tretter,V., Walker,J.etc. Fyn kinase contributes to tyrosine phosphorylation of the GABAA receptor [gamma]2 subunit. Molecular and Cellular Neuroscience 44,129-134 (2010).
20. Brandon,E.P., Idzerda,R.L., McKnight,G.S. PKA isoforms, neural pathways, and behaviour:making the connection. Current Opinion in Neurobiology 7,397-403 (1997).
21. Michel J.J.C.,Scott,J.D. AKAP MEDIATED SIGNAL TRANSDUCTION. Annu. Rev. Pharmacol. Toxicol.42,235-257 (2002).
22. Rubin CS. A kinase anchor proteins and the intracellular targeting of signals carried by cyclic AMP. Biochimica et Biophysica Acta 1224,467-479(1994).
23. Wong,W., Scott,J.D. AKAP signalling complexes:focal points in space and time. Nat Rev Mol Cell Biol 5,959-970 (2004).
24. Murphy,B.J., Rossie,S., De Jongh,K.S. etc. Identification of the sites of selective phosphorylation and dephosphorylation of the rat brain Na+ channel alpha subunit by cAMP-dependent protein kinase and phosphoprotein phosphatases. Journal of Biological Chemistry 268, 27355-27362(1993).
25. Cantrell AR, Smith RD, Goldin AL.etc Dopaminergic modulation of sodium current in hippocampal neurons via cAMP-dependent phosphorylation of specific sites in the sodium channel alpha subunit. Journal of Neuroscience 17,7330-7338 (1997).
26. Schreibmayer WF., Frohnwieser B, Dascal N.etc Beta-adrenergic modulation of currents produced by rat cardiac Na+ channels expressed in Xenopus laevis oocytes. Receptors Channels 2,339-350 (1994).
27. Frohnwieser,B., Chen,L.Q., Schreibmayer,W. etc. Modulation of the human cardiac sodium channel alpha-subunit by cAMP-dependent protein kinase and the responsible sequence domain. The Journal of Physiology 498,309-318(1997).
28. Frohnwieser B, Weigl L, Schreibmayer W. Modulation of cardiac sodium channel isoform by cyclic AMP dependent protein kinase does not depend on phosphorylation of serine 1504 in the cytosolic loop interconnecting transmembrane domains Ⅲ and IV. Pflugers Archiv European Journal of Physiology 430,751-753 (1995).
29. Tibbs.V.C. Gray.P.C.. Catterall.W.A. etc. AKAP 15 Anchors cAMP-dependent Protein Kinase to Brain Sodium Channels. Journal of Biological Chemisty 273,25783-25788 (1998).
30. Few,W.P., Scheuer,T., Catterall,W.A. Dopamine modulation of neuronal Na+channels requires binding of A kinase-anchoring protein 15and PKA by a modified leucine zipper motif. Proceedings of the National Academy of Sciences 104,5187-5192 (2007).
31. Marx,S.O. Kurokawa J, Reiken S. etc. Requirement of a Macromolecular Signaling Complex for β Adrenergic Receptor Modulation of the KCNQ1-KCNE1 Potassium Channel. Science 295,496-499 (2002).
32. Dai,S., Hall,D.D., Hell,J.W. Supramolecular Assemblies and Localized Regulation of Voltage-Gated Ion Channels. Physiological Reviews 89, 411-452(2009).
33. Chen L, Marquardt ML, Tester DJ etc. Mutation of an A-kinase-anchoring protein causes long-QT syndrome. Proceedings of the National Academy of Sciences 104,20990-20995 (2007).
34. Nara,M., Dhulipala,P.D.K., Wang,Y.X. etc. Reconstitution of β-Adrenergic Modulation of Large Conductance, Calcium-activated Potassium (Maxi-K) Channels in XenopusOocytes. Journal of Biological Chemistry 273,14920-14924 (1998).
35. Tian,L. Duncan RR, Hammond MS etc. Alternative Splicing Switches Potassium Channel Sensitivity to Protein Phosphorylation. Journal of Biological Chemistry 276,7717-7720 (2001).
36. Kim,S.J. Choi WS, Han JS etc. A Novel Mechanism for the Suppression of a Voltage-gated Potassium Channel by Glucose-dependent Insulinotropic Polypeptide. Journal of Biological Chemistry 280,28692-28700 (2005).
37. Mitterdorfer,J. Froschmayr M, Grabner M.etc. Identification of PK-A Phosphorylation Sites in the Carboxyl Terminus of L-Type Calcium Channel al Subunits. Biochemistry 35,9400-9406 (1996).
38. De Jongh KS, Merrick DK, Catterall WA. Subunits of purified calcium channels:a 212-kDa form of alpha 1 and partial amino acid sequence of a phosphorylation site of an independent beta subunit. Proc Natl Acad Sci U S A 86,8585-8589(1989).
39. Johnson BD. Brousal JP. Peterson BZ. etc. Modulation of the Cloned Skeletal Muscle L-Type Ca2+Channel by Anchored cAMP-Dependent Protein Kinase. The Journal of Neuroscience 17,1243-1255 (1997).
40. Wong,W., Scott,J.D. AKAP signalling complexes:focal points in space and time. Nat Rev Mol Cell Biol 5,959-970 (2004).
41. Hulme,J.T., Ahn,M., Hauschka,S.D.etc. A Novel Leucine Zipper Targets AKAP15 and Cyclic AMP-dependent Protein Kinase to the C Terminus of the Skeletal Muscle Ca2+ Channel and Modulates Its Function. Journal of Biological Chemistry 277,4079-4087 (2002).
42. Westphal,R.S. Tavalin SJ, Lin JW. etc. Regulation of NMDA Receptors by an Associated Phosphatase-Kinase Signaling Complex. Science 285,93-96 (1999).
43. Tingley,W.G. Ehlers MD, Kameyama K, etc. Characterization of Protein Kinase A and Protein Kinase C Phosphorylation of the N-Methyl-D-aspartate Receptor NR1 Sub unit Using Phosphorylation Site-specific Antibodies. Journal of Biological Chemistry 272,5157-5166 (1997).
44. Leonard,A.S., Hell,J.W. Cyclic AMP-dependent Protein Kinase and Protein Kinase C Phosphorylate N-Methyl-d-aspartate Receptors at Different Sites. Journal of Biological Chemistry 272,12107-12115 (1997).
45. Crump,F.T., Dillman,K.S., Craig,A.M. cAMP-Dependent Protein Kinase Mediates Activity-Regulated Synaptic Targeting of NMDA Receptors. The Journal of Neuroscience 21,5079-5088 (2001).
46. Dell'Acqua,M.L. Smith KE, Gorski JA, etc. Regulation of neuronal PKA signaling through AKAP targeting dynamics. European Journal of Cell Biology 85,627-633 (2006).
47. Tang,X., Hernandez,C.C., Macdonald,R.L. Modulation of Spontaneous and GABA-Evoked Tonic α4β3γ and a 4β3γ2L GABAA Receptor Currents by Protein Kinase A. Journal of Neurophysiology 103,1007-1019 (2010).
48. Zhang,N., Wei,W., Mody,I.etc. Altered Localization of GABAA Receptor Subunits on Dentate Granule Cell Dendrites Influences Tonic and Phasic Inhibition in a Mouse Model of Epilepsy. The Journal of Neuroscience 27, 7520-7531(2007).
49. Numann R, Catterall WA, Scheuer T. Functional modulation of brain sodium channels by protein kinase C phosphorylation. Science 254,115-118(1991).
50. Murray KT, Hu NN, Daw JR etc. Functional Effects of Protein Kinase C Activation on the Human Cardiac Na+ Channel. Circ Res 80,370-376 (1997).
51. Qu Y, Rogers JC, Tanada TN.etc A phosphorylation site in the Na+ channel required for modulation by protein kinase C. Science 254,866-868 (1991).
52. Cantrell AR, Tibbs VC, Yu FH, Murphy BJ. etc. Molecular Mechanism of Convergent Regulation of Brain Na+ Channels by Protein Kinase C and Protein Kinase A Anchored to AKAP-15. Molecular and Cellular Neuroscience 21,63-80 (2002).
53. Chen,Y., Yu,F.H., Surmeier,D.J.etc. Neuromodulation of Na+ Channel Slow Inactivation via cAMP-Dependent Protein Kinase and Protein Kinase C. Neuron 49(3),409-420.2-2-2006.
54. Tateyama,M., Kurokawa,J., Terrenoire,C.etc. Stimulation of Protein Kinase C Inhibits Bursting in Disease-Linked Mutant Human Cardiac Sodium Channels. Circulation 107,3216-3222 (2003).
55. Hoshi N, Zhang JS, Omaki M,. etc. AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists. Nat Neurosci 6,564-571 (2003).
56. Isacson,C.K., Lu,Q., Karas,R.H.etc. RACK1 is a BKCa channel binding protein. American Journal of Physiology-Cell Physiology 292, C1459-C1466 (2007).
57. McHugh,D., Sharp,E.M., Scheuer,T.etc. Inhibition of cardiac L-type calcium channels by protein kinase C phosphorylation of two sites in the N-terminal domain. Proceedings of the National Academy of Sciences of the United States of America 97,12334-12338 (2000).
58. Yokoyama CT. Myers SJ, Fu J. etc. Mechanism of SNARE protein binding and regulation of Cav2 channels by phosphorylation of the synaptic protein interaction site. Molecular and Cellular Neuroscience 28,1-17 (2005).
59. Lan JY. Skeberdis VA, Jover T. etc. Protein kinase C modulates NMDA receptor trafficking and gating. Nat Neurosci 4,382-390 (2001).
60. Chen,L., Mae Huang,L.Y. Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. Nature 356, 521-523(1992).
61. Xiong ZG, Raouf R, Lu WY. etc. Regulation of N-Methyl-d-Aspartate Receptor Function by Constitutively Active Protein Kinase C. Molecular Pharmacology 54,1055-1063 (1998).
62. Huang Y, Lu W, Ali DW. etc. CAKβ/Pyk2 Kinase Is a Signaling Link for Induction of Long-Term Potentiation in CA1 Hippocampus. Neuron 29(2), 485-496.2-1-2001.
63. Lu WY, Xiong ZG, Lei S,. etc. G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors. Nat Neurosci 2,331-338 (1999).
64. Lu,W.Y., Jackson,M.F., Bai,D.etc. In CA1 Pyramidal Neurons of the Hippocampus Protein Kinase C Regulates Calcium-Dependent Inactivation of NMDA Receptors. The Journal of Neuroscience 20,4452-4461 (2000).
65. Zheng,X., Zhang,L., Wang,A.P.etc. Protein kinase C potentiation of N-methyl-d-aspartate receptor activity is not mediated by phosphorylation of N-methyl-d-aspartate receptor subunits. Proceedings of the National Academy of Sciences 96,15262-15267 (1999).
66. Liao,G.Y., Wagner,D.A., Hsu,M.H.etc. Evidence for Direct Protein Kinase-C Mediated Modulation ofN-Methyl-d-aspartate Receptor Current. Molecular Pharmacology 59,960-964 (2001).
67. Hirai,H. Modification of AMPA receptor clustering regulates cerebellar synaptic plasticity. Neuroscience Research 39,261-267 (2001).
68. Krishek,B.J. Xie X, Blackstone C etc. Regulation of GABAA receptor function by protein kinase C phosphorylation. Neuron 12(5),1081-1095. 5-1-1994.
69. Leidenheimer,N.J., McQuilkin,S.J., Hahner,L.D.etc. Activation of protein kinase C selectively inhibits the gamma-aminobutyric acidA receptor:role of desensitization. Molecular Pharmacology 41,1116-1123 (1992).
70. Kellenberger.S., Malherbe.P., Sigel,E. Function of the alpha 1 beta 2 gamma 2S gamma-aminobutyric acid type A receptor is modulated by protein kinase C via multiple phosphorylation sites. Journal of Biological Chemistry 2677,25660-25663 (1992).
71. McDonald,B.J., Moss,S.J. Conserved phosphorylation of the intracellular domains of GABAA receptorβ2 and (33 subunits by cAMP-dependent protein kinase, cGMP-dependent protein kinase, protein kinase C and Ca2+/calmodulin type Ⅱ-dependent protein kinase. Neuropharmacology 36, 1377-1385 (1997).
72. Lin,Y.F., Angelotti,T.P., Dudek,E.M.etc. Enhancement of recombinant alpha 1 beta 1 gamma 2L gamma-aminobutyric acidA receptor whole-cell currents by protein kinase C is mediated through phosphorylation of both beta 1 and gamma 2L subunits. Molecular Pharmacology 50,185-195 (1996).
73. Poisbeau,P., Cheney,M.C., Browning,M.D.etc. Modulation of Synaptic GABAA Receptor Function by PKA and PKC in Adult Hippocampal Neurons. The Journal of Neuroscience 19,674-683 (1999).
74. Jovanovic,J.N., Thomas,P., Kittler,J.T.etc. Brain-Derived Neurotrophic Factor Modulates Fast Synaptic Inhibition by Regulating GABAA Receptor Phosphorylation, Activity, and Cell-Surface Stability. The Journal of Neuroscience 24,522-530 (2004).
75. Kmiecik,T.E., Shalloway,D. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation. Cell 49(1),65-73.4-10-1987.
76. Cartwright,C.A., Eckhart,W., Simon,S.etc. Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain. Cell 49(1),83-91. 4-10-1987.
77. Piwnica-Worms,H., Saunders,K.B., Roberts,T.M.etc. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell 49(1),75-82.4-10-1987.
78. Xu,W.Q., Doshi,A., Lei,M.etc. Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Molecular Cell 3,629-638 (1999).
79. Nada,S., Okada,M., Macauley, A. etc. Cloning of A Complementary-Dna for A Protein-Tyrosine Kinase That Specifically Phosphorylates A Negative Regulatory Site of P60C-Src. Nature 351,69-72 (1991).
80. Beacham D, Ahn M, Catterall WA.etc. Sites and molecular mechanisms of modulation of Na(v)1.2 channels by Fyn tyrosine kin. Journal of Neuroscience 27,11543-11551 (2007).
81. Ahern CA, Zhang JF, Wookalis MJ.etc. Modulation of the cardiac sodium channel NaV1.5 by Fyn, a Src family tyrosine kinase. Circ Res 96,991-998 (2005).
82. Jia Z, Jia Y, Liu B.etc. Genistein inhibits voltage-gated sodium currents in SCG neurons through protein tyrosine kinase-dependent and kinase-independent mechanisms. Pflugers Archiv European Journal of Physiology 456,857-866 (2008).
83. Holmes TC, Fadool DA, Ren R.etc. Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain. Science 274, 2089-2091 (1996).
84. Nitabach MN, Llamas DA, Araneda RC.etc. A mechanism for combinatorial regulation of electrical activity:Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors. Proc Natl AcadSci U S A 98,705-710 (2001).
85. Gamper N, Stockand JD, Shapiro MS. Subunit-specific modulation of KCNQ potassium channels by Src tyrosine kinase. Journal of Neuroscience 23,84-95 (2003).
86. Fadool DA. Tyrosine phosphorylation downregulates a potassium current in rat olfactory bulb neurons and a cloned Kv1.3 channel. Annals of the New York Academy of Sciences 855,529-532 (1998).
87. Strauss O, Rosenthal R. Dey D. etc. Effects of Protein Kinase C on Delayed Rectifier K+ Channel Regulation by Tyrosine Kinase in Rat Retinal Pigment Epithelial Cells. Investigative Ophthalmology & Visual Science 43.1645-1654(2002).
88. Hu,X.Q., Singh,N., Mukhopadhyay,D.etc. Modulation of Voltage-dependent Ca2+Channels in Rabbit Colonic Smooth Muscle Cells by c-Src and Focal Adhesion Kinase. Journal of Biological Chemistry 273,5337-5342(1998).
89. Endoh,T. Involvement of Src tyrosine kinase and mitogen-activated protein kinase in the facilitation of calcium channels in rat nucleus of the tractus solitarius by angiotensin II. The Journal of Physiology 568,851-856 (2005).
90. Strauss,O., Mergler,S., Wiederholt,M. Regulation of L-type calcium channels by protein tyrosine kinase and protein kinase C in cultured rat and human retinal pigment epithelial cells. The FASEB Journal 11,859-867 (1997).
91. Bence-Hanulec,K.K., Marshall,J., Blair,L.A.C. Potentiation of Neuronal L Calcium Channels by IGF-1 Requires Phosphorylation of the? Subunit on a Specific Tyrosine Residue. Neuron 27(1),121-131.7-1-2000.
92. Yu XM, Askalan R, Keil GJ 2nd.etc. NMD A channel regulation by channel-associated protein tyrosine kinase Src. Science 275,674-678 (1997).
93. Salter MW, Kalia LV. Src kinases:a hub for NMDA receptor regulation. Nature reviews. Neuroscience 5,317-328 (2004).
94. Macdonald DS, Weerapura M, Beazely MA. etc. Modulation of NMDA Receptors by Pituitary Adenylate Cyclase Activating Peptide in CA1 Neurons Requires Gaq, Protein Kinase C, and Activation of Src. The Journal of Neuroscience 25,11374-11384 (2005).
95. Yang,M., Leonard,J.P. Identification of mouse NMDA receptor subunit NR2A C-terminal tyrosine sites phosphorylated by coexpression with v-Src. Journal of Neurochemistry 77,580-588 (2001).
96. Reiss,K. Maretzky T, Haas IG etc. Regulated ADAM10-dependent Ectodomain Shedding of y-Protocadherin C3 Modulates Cell-Cell Adhesion. Journal of Biological Chemistry 281.21735-21744 (2006).
97. Cheung.H.H., Teves,L., Wallace.M.C.etc. Inhibition of protein kinase C reduces ischemia-induced tyrosine phosphorylation of the N-methyl-d-aspartate receptor. Journal of Neurochemistry 86.1441-1449 (2003).
98. Hayashi,T., Umemori.H., Mishina,M.etc. The AMPA receptor interacts with and signals through the protein tyrosine kinase Lyn. Nature 397,72-76(1999).
99. Hayashi,T., Huganir,R.L. Tyrosine Phosphorylation and Regulation of the AMPA Receptor by Src Family Tyrosine Kinases. The Journal of Neuroscience 24,6152-6160 (2004).
100. Wan Q, Man HY, Braunton J. etc. Modulation of GABAA Receptor Function by Tyrosine Phosphorylation of β Subunits. The Journal of Neuroscience 17,5062-5069 (1997).
101. Valenzuela,C.F., Machu TK, McKernan RM. etc. Tyrosine kinase phosphorylation of GABAA receptors. Molecular Brain Research 31,165-172(1995).
102. Moss,S.J., Gorrie,G.H., Amato,A.etc. Modulation of GABAA receptors by tyrosine phosphorylation. Nature 377,344-348 (1995).
103. Brandon,N.J., Delmas.P., Hill,J.etc. Constitutive tyrosine phosphorylation of the GABAA receptor γ2 subunit in rat brain. Neuropharmacology 41, 745-752(2001).
104. Boxall,A.R. GABAergic mIPSCs in rat cerebellar Purkinje cells are modulated by TrkB and mGluR1-mediated stimulation of Src. The Journal of Physiology 524,677-684 (2000).
105. Jurd,R., Tretter,V., Walker,J.etc. Fyn kinase contributes to tyrosine phosphorylation of the GABAA receptor γ2 subunit. Molecular and Cellular Neuroscience 44,129-134 (2010).
106. Takashi Yamauchi. Neuronal Ca2+/Calmodulin-Dependent Protein Kinase Ⅱ—Discovery, Progress in a Quarter of a Century, and Perspective: Implication for Learning and Memory. Biological & Pharmaceutical Bulletin 28,1342-1354 (2005).
107. Yamauchi,T., Ohsako.S., Deguchi, T. Expression and characterization of calmodulin-dependent protein kinase Ⅱ from cloned cDNAs in Chinese hamster ovary cells. Journal of Biological Chemistry 264.19108-19116 (1989).
108. Puertollano,R., Alonso,M.A. A Short Peptide Motif at the Carboxyl Terminus Is Required for Incorporation of the Integral Membrane MAL Protein to Glycolipid-enriched Membranes. Journal of Biological Chemistry 273,12740-12745 (1998).
109. Ando S, Tokui T, Yamauchi T. etc. Evidence that Ser-82 is a unique phosphorylation site on vimentin for CA2+-calmodulin-dependent protein kinase Ⅱ. Biochemical and Biophysical Research Communications 175, 955-962(1991).
110. Ohsako,S., Nakazawa,H., Sekihara,S.etc. Role of Threonine-286 as Autophosphorylation Site for Appearance of Ca2+-Independent Activity of Calmodulin-Dependent Protein Kinase Ⅱ α Subunit. Journal of Biochemistry 109,137-143 (1991).
111. Wagner S, Dybkova N, Rasenack EC.etc. Ca2+/calmodulin-dependent protein kinase Ⅱ regulates cardiac Na+ channels. J Clin Invest 116,3127-3138(2006).
112. Aiba,T. Hesketh GG,Liu T. etc. Na+ channel regulation by Ca2+/calmodulin and Ca2+/calmodulin-dependent protein kinase Ⅱ in guinea-pig ventricular myocytes. Cardiovascular Research 85,454-463 (2010).
113. Ganetzky,B.A., Robertson,G.A., WILSON,G.F.etc. The Eag Family of K+ Channels in Drosophila and Mammals. Annals of the New York Academy of Sciences 868,356-369 (1999).
114. Wang,Z., Willson,G.F., Griffith,L.C. Calcium/Calmodulin-dependent Protein Kinase Ⅱ Phosphorylates and Regulates the Drosophila Eag Potassium Channel. Journal of Biological Chemistry 277,24022-24029 (2002).
115. Zhou Y, Schopperle WM, Murrey H. etc. A Dynamically Regulated 1433, Slob, and Slowpoke Potassium Channel Complex in Drosophila Presynaptic Nerve Terminals. Neuron 22(4),809-818.4-1-1999.
116. Lee TS, Karl R, Moosmang S. etc. Calmodulin Kinase Ⅱ Is Involved in Voltage-dependent Facilitation of the L-type Cav1.2 Calcium Channel. Journal of Biological Chemistry 281,25560-25567 (2006).
117. Ertel EA, Campbell KP, Harpold MM. etc. Nomenclature of Voltage-Gated Calcium Channels. Neuron 25,533-535 (2000).
118. Jiang X, Lautermilch NJ, Watari H. etc. Modulation of CaV2.1 channels by Ca2+/calmodulin-dependent protein kinase Ⅱ bound to the C-terminal domain. Proceedings of the National Academy of Sciences 105,341-346 (2008).
119. Welsby PJ, Wang H, Wolfe JT. etc. A Mechanism for the Direct Regulation of T-Type Calcium Channels by Ca2+/Calmodulin-Dependent Kinase Ⅱ. The Journal of Neuroscience 23,10116-10121 (2003).
120. Yao J, Davies LA, Howard JD. etc. Molecular basis for the modulation of native T-type Ca2+ channels in vivo by Ca2+/calmodulin-dependent protein kinase Ⅱ. J Clin Invest 116,2403-2412 (2006).
121. Kennedy,M.B., Bennett,M.K., Erondu,N.E. Biochemical and immunochemical evidence that the "major postsynaptic density protein" is a subunit of a calmodulin-dependent protein kinase. Proceedings of the National Academy of Sciences 80,7357-7361 (1983).
122. Strack,S., McNeill,R.B., Colbran,R.J. Mechanism and Regulation of Calcium/Calmodulin-dependent Protein Kinase Ⅱ Targeting to the NR2B Subunit of the N-Methyl-d-aspartate Receptor. Journal of Biological Chemistry 275,23798-23806 (2000).
123. Leonard,A.S., Lim,I.A., Hemsworth,D.E.etc. Calcium/calmodulin-dependent protein kinase II is associated with the N-methyl-d-aspartate receptor. Proceedings of the National Academy of Sciences 96,3239-3244 (1999).
124. Gardoni,F. Schrama LH, van Dalen JJ. etc. [alpha]CaMKII binding to the C-terminal tail of NMDA receptor subunit NR2A and its modulation by autophosphorylation. FEBS Letters 456,394-398 (1999).
125. Bayer,K.U., De Koninck.P., Leonard.A.S.etc. Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature 411.801-805 (2001).
126. Lisman.J.. Schulman.H.. Cline.H. The molecular basis of CaMKII function in synaptic and behavioural memory. Nat Rev Neurosci 3,175-190 (2002).
127. Lieberman.D.N., Mody,I. Casein kinase-Ⅱ regulates NMDA channel function in hippocampal neurons. Nat Neurosci 2,125-132 (1999).
128. Barria,A., Malinow,R. NMD A Receptor Subunit Composition Controls Synaptic Plasticity by Regulating Binding to CaMKII. Neuron 48(2),289-301.10-20-2005.
129. Barria,A., Muller,D., Derkach,V.etc. Regulatory Phosphorylation of AMPA-Type Glutamate Receptors by CaM-KII During Long-Term Potentiation. Science 276,2042-2045 (1997).
130. Bevilaqua,L.R., Medina,J.H., Izquierdo,I.etc. Memory consolidation induces N-methyl-d-aspartic acid-receptor- and Ca2+/calmodulin-dependent protein kinase Ⅱ-dependent modifications in [alpha]-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor properties. Neuroscience 136,397-403 (2005).
131. Macica CM, Kaczmarek LK. Casein kinase 2 determines the voltage dependence of the Kv3.1 channel in auditory neurons and transfected cells. Journal of Neuroscience 21,1160-1168 (2001).
132. Mackenzie FE, Parker A, Parkinson NJ. etc. Analysis of the mouse mutant Cloth-ears shows a role for the voltage-gated sodium channel Scn8a in peripheral neural hearing loss. Genes, Brain and Behavior 8,699-713 (2009).