Effects of Astragaloside IV on Action Potentials and Ionic Currents in Guinea-Pig Ventricular Myocytes

Effects of Astragaloside IV on Action Potentials and Ionic Currents in Guinea-Pig Ventricular Myocytes
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黄芪甲苷对豚鼠心室肌​​细胞动作电位和离子电流的影响

DOI:
10.1248/bpb.b12-00655
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发表时间:
2013-04-01
影响因子:
2
通讯作者:
Hao, Liying
Hao, Liying
中科院分区:
医学4区
文献类型:
--
作者:
Zhao, Meimi;Zhao, Jinsheng;Hao, Liying

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黄芪皂苷IV(AS-IV)是黄芪的主要活性成分之一,对心血管系统有多种作用。然而,其电生理机制尚不清楚。在本研究中,我们采用全细胞膜片钳技术,观察了AS-IV对豚鼠心室肌细胞动作电位和膜电流的影响。AS-IV在三个受试浓度下均能延长动作电位时程。在1×10~(-6)M时达到最大效应,在此浓度下,As-IV使95%复极时程由313.1±38.9ms延长至785.3±83.7ms。AS-IV在1×10(-6)M时也能增强内向整流钾电流(I-K1),抑制延迟整流钾电流(I-K)。As-IV(1×10~(-6)M)使电压依赖性钙通道电流(I-Cal)峰值由-607.3+/-37.5pA降至-321.1+/-38.3pA。但AS-IV对Na+电流无明显影响。综上所述,AS-IV可延长豚鼠心室肌细胞动作电位时程,其机制可能与其抑制K-K有关。AS-IV还通过抑制I-Cal影响钙信号转导。
Astragaloside IV (AS-IV) is one of the main active constituents of Astragalus membranaceus, which has various actions on the cardiovascular system. However, its electrophysiological mechanisms are not clear. In the present study, we investigated the effects of AS-IV on action potentials and membrane currents using the whole-cell patch clamp technique in isolated guinea-pig ventricular myocytes. AS-IV prolonged the action potential duration (APD) at all three tested concentrations. The peak effect was achieved with 1x10(-6)M, at which concentration AS-IV significantly prolonged the APD at 95% repolarization from 313.1 +/- 38.9 to 785.3 +/- 83.7 ms. AS-IV at 1x10(-6) M also enhanced the inward rectifier K+ currents (I-K1) and inhibited the delayed rectifier K+ currents (I-K). AS-IV (1x10(-6) M) strongly depressed the peak of voltage-dependent Ca2+ channel current (I-CaL) from -607.3 +/- 37.5 to -321.1 +/- 38.3 pA. However, AS-IV was not found to affect the Na+ currents. Taken together, AS-IV prolonged APD of guinea-pig ventricular myocytes, which might be explained by its inhibition of I-K. AS-IV also influences Ca2+ signaling through suppressing I-CaL.