川芎嗪对大鼠心室肌细胞L型钙通道的影响。

Effect of tetramethyl pyrazine on L-type calcium channel in rat ventricular myocytes.

作者信息

Zou L Y, Hao X M, Zhang G Q, Zhang M, Guo J H, Liu T F

机构信息

Electrophysiological Department of the Second Affiliated Hospital, Peking University, Beijing, China.

出版信息

Can J Physiol Pharmacol. 2001 Jul;79(7):621-6.

PMID:11478596

Abstract

To elucidate possible ionic mechanisms of antimyocardial ischemia and antiarrythmia of tetramethyl pyrazine (TP), we studied L-type Ca2+ currents (I(Ca.L)) in adult rat ventricular myocytes using the whole-cell patch-clamp technique. The results showed: (i) under physiological conditions, 0.25 mmol/L TP decreased amplitude of I(Ca.L) to 60.6% and this inhibition was increased with increasing concentration of TP. ID50 was 0.20 mmol/L. (ii) The Ca2+-antagonistic effect of TP was voltage-dependent. A marked negative shift of the steady-state inactivation curve was observed with long (10 s) conditioning prepulses, but not with short (350 ms) ones. (iii) The time course of inhibition during TP treatment was increased with an increase in drug concentration, and recovery from TP-induced inactivation of I(Ca.L) was slower than in control cases. (iv) Tonic block and use-dependent block with TP treatment, which was induced by increasing the frequency of stimulation, occurred. We suggest that TP inhibits the I(Ca.L) mainly by binding to inactivated Ca2+ channels. The high affinity of TP for the inactivated state of I(Ca.L) may play an important role in developing therapies for pathological conditions.

摘要

为阐明川芎嗪（TP）抗心肌缺血和抗心律失常的可能离子机制，我们采用全细胞膜片钳技术研究了成年大鼠心室肌细胞的L型钙电流（I(Ca.L)）。结果显示：（i）在生理条件下，0.25 mmol/L的TP使I(Ca.L)的幅度降低至60.6%，且这种抑制作用随TP浓度的增加而增强。半数抑制浓度（ID50）为0.20 mmol/L。（ii）TP的钙拮抗作用具有电压依赖性。使用长时（10 s）的预处理脉冲可观察到稳态失活曲线明显负向移位，而短时（350 ms）的预处理脉冲则无此现象。（iii）TP处理过程中的抑制时程随药物浓度增加而延长，且TP诱导的I(Ca.L)失活后的恢复比对照组慢。（iv）出现了TP处理导致的强直阻滞和使用依赖性阻滞，后者是通过增加刺激频率诱导产生的。我们认为，TP主要通过与失活的钙通道结合来抑制I(Ca.L)。TP对I(Ca.L)失活状态的高亲和力可能在病理状况的治疗开发中发挥重要作用。