不同旋体氨氯地平对大鼠心室肌细胞L-型钙离子流的影响

目的 探讨不同旋体氨氯地平对大鼠心室肌细胞L-型钙离子流(ICa-L)及通道动力学参数影响. 方法 采用酶消化法分离大鼠心室肌细胞,以全细胞膜片钳技术分别记录加入0.1、0.5、1、5和10 μmol/L左旋、右旋和混旋氨氯地平后大鼠心室肌细胞ICa-L、峰值电流、Ⅰ-Ⅴ曲线、稳态激活曲线、稳态失活曲线和失活后恢复曲线的变化. 结果 加入0.1、0.5、1、5和10 μmol/L左旋和混旋氨氯地平后,左旋氨氯地平对ICa-L阻滞分别为(1.5±0.2)%、(25.4±5.3)%、(65.2±7.3)%、(78.4 ±8.1)%和(94.2±5.0)%,混旋氨氯地平对ICa-L阻滞分别为(0.9±0.1)%、(10.4±3.2)%、(69.1±5.3)%、(75.2±7.0)%和(81.6±6.4)%,Ⅰ-Ⅴ曲线上移、稳态激活曲线和稳态失活曲线左移、失活后恢复时间延长(P＜0.05),且相同浓度左旋氨氯地平对ICa-L.和通道动力学参数影响比混旋氨氯地平更明显(P＜0.05),但不同浓度右旋氨氯地平对ICa-L及通道动力学参数均无影响(P＞0.05). 结论 左旋和混旋氨氯地平对ICa-L有阻滞作用,而右旋氨氯地平对ICa-L无阻滞作用.

Effects of different amlodipine isomers on L-type calcium current of rat ventricular myocytes

0bjective To investigate the effects of different amlodipine isomers on L-type calcium current(Ica-L)and kinetics of rat ventricular myocytes.Methods Rat ventricular myocytes were isolated by enzyme digestion.Ica-L,peak currents,Ⅰ-Ⅴ curves,steady state activation curves,steady state inactivation curves and recovery curves from inactivation with S-amlodipine,R-amlodipine and R,S- amlodipine at concentrations of 0.1,0.5,1,5,and 10 μmol/L were recorded by whole-cell patch clamp configuration.Results At the concentrations of 0.1,0.5,1,5,and 10 μmol/L,Ica-L were blocked in a dose-dependent manner by S-amlodipine(1.5 ±0.2)%,(25.4 ±5.3)%,(65.2 ±7.3)%,(78.4 ± 8.1)%, and(94.2 ±5.0)%]and by R,S-amlodipine(0.9 ±0.1)%,(10.4 ±3.2)%,(69.1 ± 5.3)%, (75.2 ±7.0)%,and (81.6 ±6.4)%].Ⅰ-Ⅴ curves were significantly shifted upward,steady state activation and inactivation curves were significantly shifted to left by S-amlodipine and R,S-amlodipine (0.1μmol/L to 10μmol/L).Recovery time from inactivation was also significantly prolonged by S-amlodipine(210.1 ±19.5)ms,(225.2 ±21.3)ms,(241.7 ±20.3)ms,(252.3±24.2)ms,and (282.6 ±23.2)ms] and by R,S-amlodipine(208.7 ±17.4)ms,(215.8±18.3)ms,(225.2±21.3)ms,(235.8 ±22.7)ms,and(252.3 ±24.2)ms]in a dose-dependent manner.The observed effects of S-amlodipine were more potent than those of R,S-amlodipine(P<0.05).However,all these parameters were not affected by R-amlodipine at various concentrations (P>0.05).Conclusion L-type calcium cnrrent of rat ventricular myocytes could be blocked by R,S-amlodipine and S-amlodipine in a dose-dependent manner.