参松养心胶囊对大鼠心室肌细胞L-型钙电流和钾电流的抑制作用
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摘要
目的:探讨参松养心胶囊对大鼠心室肌细胞L-型钙电流(Ica,L)和瞬时外向钾电流(Ito)的抑制作用。方法:酶解法分离大鼠心室肌细胞,使用参松养心溶液(0.5 mg/100 m L,0.5%)灌流心室肌细胞,利用全细胞膜片钳技术记录Ica,L和Ito,在细胞破膜后的20 min内记录所有数据,对每个细胞给药前后做自身对照,观察参松养心溶液对Ica,L和Ito通道电流的影响。结果:0.5%的参松养心溶液对Ica,L和Ito均有抑制作用,参松养心溶液对Ito的缓慢电流成分Itos无明显作用,但可以明显抑制Ito的快速电流成分Itof。在-10 m V测试电压下,在0.5%的参松养心溶液作用后,Ica,L的最大激活峰值电流密度从(-8.64+-2.43)p A/p F降为(-5.92+-2.15)p A/p F,抑制率为31.85%+10.25%,电流密度-电压(I-V)曲线上移;在-60 m V测试电压下,在0.5%的参松养心溶液作用后,Itof的最大激活峰值电流密度从(23.53+3.31)p A/p F降为(16.86+2.34)p A/p F,抑制率为(28.33+10.59)%,I-V曲线下移。参松养心溶液不改变Ica,L的通道动力学,但会使Ito通道失活后的恢复变慢。结论:参松养心溶液对Ica,L和Ito均有明显的抑制作用。
Objective: Explore the inhibitory effect of Shensong Yangxin capsule on rat ventricular myocyte L- type calcium current( Ica,L) and transient outward potassium current( Ito). Methods: Using enzymatic hydrolysis to separated rat ventricular muscle cells,using Shensong Yangxin solution( 0. 5 mg/100 ml,0. 5%) perfusion ventricular muscle cells,using whole cell patch clamp technique to record the Ica,L and Ito,the cell membrane within 20 min after record all data,for each cell to do self-reflection,before and after observation and Shensong Yangxin solution of Ica,L and the impact of Ito channel current. Result: 0. 5% Shensong Yangxin solution has inhibitory effect on Ica,L and Ito,in particular,and Shensong Yangxin solution of Ito slow current component itqs has no obvious effect,but can obviously inhibitory the Ito Itof the rapid current components. Under-10 m V test voltage,after 0. 5% role and Shensong Yangxin solution,Ica,L biggest activated peak current density from( 8. 64 + 2. 43) p A/p F reduced to( 5. 92 + 2. 15) p A/p F,the inhibitory rate of( 31. 85% + 31. 85%),current density and voltage( I- V) curves upward; Under 60 m V test voltage,after 0. 5% of the role and shensong yangxin solution,Itof biggest activated peak current density from( 23. 53 + 3. 31) p A /p F is( 16. 86 + 2. 34) p A/p F,the inhibitory rate of( 28. 33% + 28. 33%),the i-v curve down. And Shensong Yangxin solution without changing the Ica,L channel dynamics,but can make the Ito channel after the deactivation of slow recovery. Conclusion: Shensong Yangxin solution has obvious inhibitory effect on Ica,L and Ito.
Objective: Explore the inhibitory effect of Shensong Yangxin capsule on rat ventricular myocyte L- type calcium current( Ica,L) and transient outward potassium current( Ito). Methods: Using enzymatic hydrolysis to separated rat ventricular muscle cells,using Shensong Yangxin solution( 0. 5 mg/100 ml,0. 5%) perfusion ventricular muscle cells,using whole cell patch clamp technique to record the Ica,L and Ito,the cell membrane within 20 min after record all data,for each cell to do self-reflection,before and after observation and Shensong Yangxin solution of Ica,L and the impact of Ito channel current. Result: 0. 5% Shensong Yangxin solution has inhibitory effect on Ica,L and Ito,in particular,and Shensong Yangxin solution of Ito slow current component itqs has no obvious effect,but can obviously inhibitory the Ito Itof the rapid current components. Under-10 m V test voltage,after 0. 5% role and Shensong Yangxin solution,Ica,L biggest activated peak current density from( 8. 64 + 2. 43) p A/p F reduced to( 5. 92 + 2. 15) p A/p F,the inhibitory rate of( 31. 85% + 31. 85%),current density and voltage( I- V) curves upward; Under 60 m V test voltage,after 0. 5% of the role and shensong yangxin solution,Itof biggest activated peak current density from( 23. 53 + 3. 31) p A /p F is( 16. 86 + 2. 34) p A/p F,the inhibitory rate of( 28. 33% + 28. 33%),the i-v curve down. And Shensong Yangxin solution without changing the Ica,L channel dynamics,but can make the Ito channel after the deactivation of slow recovery. Conclusion: Shensong Yangxin solution has obvious inhibitory effect on Ica,L and Ito.
引文
[1]张利娟,李常红,盛怀汤.参松养心胶囊改善冠心病患者室性早搏的临床观察[J].中国中医基础医学杂志,2013,19(7):790-791.
[2]Lin Zhang,Jeff Kelley,Glen Schmeisser,et al.Complex formation between junction,triadin,calsequestrin,and the ryanodine.Proteins of the cardiac junctional sarcoplasmic reticulum membrane[J].J Biol Chem,1997,272(37):23389-22297.
[3]冉玉琴,李宁,王蓉蓉,等.丹酚酸B对大鼠心室肌细胞瞬时外向钾电流和L型钙电流的阻滞作用[J].中国心脏起搏与心电生理杂志,2010,24(4):344-348.
[4]Hiroshi Irie,Junyuan Gao,Glenn R.Gandette,et al.Both metabolic inhibition and mitochondrial KATP channel opening are myoprotective and initiate a compensatory sarcolemmal outward membrane current[J].Circulation,2003,108(9):341-347.
[5]Haibo He,Mengqiong Shi,Xiaowei Zeng,et al.6 expression and enhanced endothelin receptor signaling associated with arrhymogenesis in myocardial infarction rat[J].Phytother Research,2008,22(8):1-11.
[6]陆洁,陆有为,孙珏,等.参松养心胶囊治疗老年缓慢心率失常的疗效评价[J].中国中医基础医学杂志,2012,18(12):1368-1370.
[7]Z.Papp,N.Peineau,G.Szigeti,J.Argibay and L.Kovacs.Calcimu-dependent modulation of the plateau phase of action potential in isolated ventricular cells of rabbit heart[J].Acta Physiol Scand,1999,167(2):119-129.
[8]Li GR,Feng J,Carrier M,et al.Transmural heterogeneity of action potential and Ito in myocytes isolated from the human right ventricle[J].Am J Physiol,1998,275(2):H369-H377.
[9]胡昊,唐海沁,李洁华,等.参松养心胶囊抗心律失常的疗效和安全性系统评价[J].中国循证医学杂志,2011,11(2):168-173.
[10]苏庆丰,张林虎.参松养心胶囊治疗慢性心衰合并室性早搏[J].中西医结合心脑血管病杂志,2011,9(9):1138-1139.
[2]Lin Zhang,Jeff Kelley,Glen Schmeisser,et al.Complex formation between junction,triadin,calsequestrin,and the ryanodine.Proteins of the cardiac junctional sarcoplasmic reticulum membrane[J].J Biol Chem,1997,272(37):23389-22297.
[3]冉玉琴,李宁,王蓉蓉,等.丹酚酸B对大鼠心室肌细胞瞬时外向钾电流和L型钙电流的阻滞作用[J].中国心脏起搏与心电生理杂志,2010,24(4):344-348.
[4]Hiroshi Irie,Junyuan Gao,Glenn R.Gandette,et al.Both metabolic inhibition and mitochondrial KATP channel opening are myoprotective and initiate a compensatory sarcolemmal outward membrane current[J].Circulation,2003,108(9):341-347.
[5]Haibo He,Mengqiong Shi,Xiaowei Zeng,et al.6 expression and enhanced endothelin receptor signaling associated with arrhymogenesis in myocardial infarction rat[J].Phytother Research,2008,22(8):1-11.
[6]陆洁,陆有为,孙珏,等.参松养心胶囊治疗老年缓慢心率失常的疗效评价[J].中国中医基础医学杂志,2012,18(12):1368-1370.
[7]Z.Papp,N.Peineau,G.Szigeti,J.Argibay and L.Kovacs.Calcimu-dependent modulation of the plateau phase of action potential in isolated ventricular cells of rabbit heart[J].Acta Physiol Scand,1999,167(2):119-129.
[8]Li GR,Feng J,Carrier M,et al.Transmural heterogeneity of action potential and Ito in myocytes isolated from the human right ventricle[J].Am J Physiol,1998,275(2):H369-H377.
[9]胡昊,唐海沁,李洁华,等.参松养心胶囊抗心律失常的疗效和安全性系统评价[J].中国循证医学杂志,2011,11(2):168-173.
[10]苏庆丰,张林虎.参松养心胶囊治疗慢性心衰合并室性早搏[J].中西医结合心脑血管病杂志,2011,9(9):1138-1139.
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