摘要
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.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2008年第5期425-429,共5页
Chinese Journal of Cardiology
关键词
氨氯地平
钙通道
膜片钳术
Amlodipine
Calcium channels
Patch-clamp techniques