（S）-氨氯地平和（R）-氨氯地平对大鼠心室肌细胞L型钙通道电流及主动脉平滑肌细胞胞质钙的影响。

Effects of (S)-amlodipine and (R)-amlodipine on L-type calcium channel current of rat ventricular myocytes and cytosolic calcium of aortic smooth muscle cells.

作者信息

Wang Ru-Xing, Jiang Wen-Ping, Li Xiao-Rong, Lai Li-Hong

机构信息

Department of Cardiology, First Affiliated Hospital of Nanjing Medical University in Wuxi, China.

出版信息

Pharmazie. 2008 Jun;63(6):470-4.

DOI:

PMID:18604992

Abstract

OBJECTIVE

Amlodipine (Aml) has R- and S-isomers with different pharmacological effects. However, no data are available on the influence of (S)-Aml and (R)-Aml on L-type calcium channel current (I(Ca-L)) or cytosolic calcium (Ca2+). This study is to investigate effects on I(Ca-L) and cytosolic Ca2+.

METHODS

I(Ca-L), peak currents, I-V curves, steady state activation curves, steady state inactivation curves and recovery curves from inactivation with (S)-Aml and (R)-Aml were recorded by whole-cell patch clamp configuration. Cytosolic Ca2+ of smooth muscle cells was assayed by Fura-2/AM.

RESULTS

At the concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L, 1.5 +/- 0.2%, 25.4 +/- 5.3%, 65.2 +/- 7.3%, 78.4 +/- 8.1%, and 94.2 +/- 5.0% of I(Ca-L) were blocked by (S)-Aml. I-V curves were shifted upward. Half-activation voltages were -16.01 +/- 1.65 mV, -17.61 +/- 1.60 mV, -20.17 +/- 1.46 mV, -21.87 +/- 1.69 mV and -24.09 +/- 1.87 mV (P < 0.05). Half-inactivation voltages were -27.16 +/- 4.48 mV, -28.69 +/- 4.52 mV, -31.19 +/- 4.17 mV, -32.63 +/- 4.34 mV and -35.16 +/- 4.46 mV (P < 0.05). Recovery time were prolonged gradually (P < 0.05). 10.3 +/- 1.2%, 35.2 +/- 3.5%, 60.1 +/- 5.0%, 78.9 +/- 6.1%, and 91.2 +/- 7.6% of cytosolic Ca2+ were reduced at different concentrations (P < 0.05). However, (R)-Aml at different concentrations had no effect on I(Ca-L) and cytosolic Ca2+ (P > 0.05).

CONCLUSION

Only (S)-Aml has calcium channel blockade activity, while (R)-Aml has none of the pharmacologic actions associated with CCBs.

摘要

目的

氨氯地平（Aml）有R-和S-两种异构体，其药理作用不同。然而，关于（S）-Aml和（R）-Aml对L型钙通道电流（I(Ca-L)）或细胞溶质钙（Ca2+）影响的数据尚无报道。本研究旨在探讨其对I(Ca-L)和细胞溶质Ca2+的影响。

方法

采用全细胞膜片钳记录（S）-Aml和（R）-Aml作用下的I(Ca-L)、峰值电流、I-V曲线、稳态激活曲线、稳态失活曲线以及失活后恢复曲线。用Fura-2/AM检测平滑肌细胞的细胞溶质Ca2+。

结果

在0.1、0.5、1、5和10 μmol/L浓度下，（S）-Aml分别阻断1.5±0.2%、25.4±5.3%、65.2±7.3%、78.4±8.1%和94.2±5.0%的I(Ca-L)。I-V曲线向上移位。半数激活电压分别为-16.01±1.65 mV、-17.61±1.60 mV、-20.17±1.46 mV、-21.87±1.69 mV和-24.09±1.87 mV（P<0.05）。半数失活电压分别为-27.16±4.48 mV、-28.69±4.52 mV、-31.19±4.17 mV、-32.63±4.34 mV和-35.16±4.46 mV（P<0.05）。恢复时间逐渐延长（P<0.05）。不同浓度下细胞溶质Ca2+分别降低10.3±1.2%、35.2±3.5%、60.1±5.0%、78.9±6.1%和91.2±7.6%（P<0.05）。然而，不同浓度的（R）-Aml对I(Ca-L)和细胞溶质Ca2+无影响（P>0.05）。