不同旋体氨氯地平对大鼠心室肌细胞动作电位和L-型钙离子流的影响

目的 探讨不同旋体氨氯地平(amlodipine,Aml)对大鼠心室肌细胞动作电位和L-型钙离子流(ICa-L)的影响.方法 采用酶消化法获得大鼠耐钙心室肌细胞,以全细胞膜片钳技术分别观察并记录加入0.1、0.5、1、5和10 μmol/L左旋、右旋和混旋Aml后大鼠心室肌细胞动作电位、ICa-L及通道动力学参数的变化.结果 (1)加入0.1、0.5、1、5和10 μmol/L左旋、右旋和混旋Aml后,动作电位最大上升速率、动作电位幅度和超射无明显变化(P＞0.05);但左旋和混旋Aml对动作电位时限影响表现为随着浓度增加动作电位时限逐渐缩短(P＜0.05),且相同浓度的左旋Aml对动作电位时限影响比混旋Aml更明显(P＜0.05),而不同浓度右旋Aml对动作电位时限无影响(P＞0.05).(2)加入0.1、0.5、1、5和10 μmol/L左旋和混旋Aml后,ICa-L及峰值电流呈浓度依赖性降低、稳态激活曲线和稳态失活曲线左移(P＜0.05),且相同浓度左旋Aml对Ica-L和通道动力学参数影响比混旋Aml更明显(P＜0.05),但不同浓度右旋Aml对,ICa-L及通道动力学参数均无影响(P＞0.05).结论 左旋和混旋Aml对L-型钙通道有阻滞作用,表现为,ICa-L降低,动作电位时限缩短,而右旋Aml对L-型钙通道无阻滞作用,因而对ICa-L和动作电位时限无影响.

Effects of different amlodipine isomers on action potential and L-type calcium current of rat

Objective To investigate the effects of different awlodipine (Aml) isomers on action potential (AP) and L-type calcium current (ICa-L) of rat. Methods Calcium-tolerant ventricular myocytes were isolated by enzyme digestion. Changes of AP, ICa-L and channel kinetic parameters with S-Aml, R-Aml and R,S-Aml at concentrations of 0. 1,0. 5, 1,5, and 10 μmol/L were recorded respectively by whole-cell configuration patch clamp. Results (1) AP maximal depolarization velocity, AP amplitude and overshoot were no significant changes with S-Aml, R-Aml and R, S-Aml at concentrations of 0. 1,0. 5, 1,5, and 10 μmol/L(P ＞0. 05). AP durations (APDs) were shortened gradually with the increase of S-Aml and R, S-Aml concentrations from 0. 1 μmo]/L to 10 μmol/L (P＜0. 05), and APDs with S-Aml were much shorter than those at the same concentrations of R, S-Aml (P＜0. 05). However, R-Aml at different concentrations had no effects on APDs (P ＞ 0. 05). (2)ICa-L and peak currents were reduced gradually, steady state activation and inactivation curves were shifted to the left with the increase of S-Aml and R, S-Aml concentrations from 0. 1 μmol/L to 10 μmol/L (P＜0. 05). ICa-L and channel kinetic parameters with S-Aml were changed more significantly than those at the same concentrations of R, S-Aml (P＜0. 05). However, R-Aml at different concentrations had no effects on ICa-L and channel kinetic parameters (P ＞ 0.05). Conclusion R, S-Aml and S-Aml have blockage effects on L-type calcium channel, and therefore reduce ICa-L and shorten APDs. However, R-Aml has no pharmacological actions on L-type calcium channel, and has no effects on ICa-L and APDs.