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

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

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10μmoL／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10μmol／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。

Objective To investigate the effects of different amledipine 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 10μmol/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 current of rat ventricular myocytes could be blocked by R, S-amlodipine and S-amlodipine in a dose-dependent manner.