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川芎嗪对猪冠状动脉平滑肌细胞大电导钙激活钾通道的作用

杨艳艳, 杨艳, 曾晓荣, 刘智飞, 蔡芳, 李妙龄, 周文, 裴杰

泸州医学院心肌电生理学研究室. 泸州 646000

摘要

该工作旨在研究川芎嗪对猪冠状动脉平滑肌细胞钾通道的作用，为阐明其扩张冠状动脉血管的机制提供实验依据。采用膜片钳细胞贴附式和内面向外式记录方式观察川芎嗪对猪冠状动脉平滑肌细胞大电导钙激活钾通道(large--conductance Ca~(2+)--activated potassium channels, BK_(Ca) channels)的作用，分别用蛋白激酶A (protein kinase A, PKA)抑制剂H--89和蛋白激酶G (protein kinase G, PKG)抑制剂KT--5823处理细胞，再观察川芎嗪对BK_(Ca)通道作用的变化。结果表明在研究的0.73---8.07 mmol/L 浓度范围，川芎嗪可以剂量依赖性地激活BKCa通道，使通道的开放概率从 (0.01±0.003) 增加到(0.03±0.01)---(1.21±0.18) ({sl P}<0.01，{sl n}=10)，使通道平均关闭时间从(732.33±90.67) ms降低到(359.67±41.30)---(2.96±0.52) ms ({sl P}<0.01，{sl n}=10)。川芎嗪的这种激活作用在浴液游离钙离子浓度接近0 mmol/L时也存在。PKA的特异性抑制剂H--89 (3 #mu#mol/L) 和PKG的特异性抑制剂KT--5823 (1 #mu#mol/L)对川芎嗪激活BK_(Ca)通道的作用无影响。以上结果提示：川芎嗪能直接激活冠状动脉平滑肌BK_(Ca)通道，这种作用可能是川芎嗪扩张冠状动脉血管的一种重要机制。

关键词： 川芎嗪; 大电导钙激活钾通道; 猪冠状动脉平滑肌细胞; 膜片钳技术

Effects of tetramethylpyrazine on large--conductance Ca~(2+)--activated potassium channels in porcine coronary artery smooth muscle cells

Yang Yanyan, Yang Yan, Zeng Xiaorong, Liu Zhifei, Cai Fang, Li Miaoling, Zhou Wen, Pei Jie

Institute of Myocardial Electrophysiology, Luzhou Medical College. Luzhou 646000, China

Abstract

The aim of the present study was to examine the effects of tetramethylpyrazine (TMP) on large-conductance Ca~(2+)-activated potassium channels (BK_(Ca) channels) in porcine coronary artery smooth muscle cells, in order to provide the experimental evidence for expounding the mechanism of TMP in dilating coronary artery. Cell-attached and inside-out single channel recording techniques were used to observe the effects of TMP on BK_(Ca) channels as well as the effects after the cells were treated by protein kinase A (PKA) inhibitor or protein kinase G (PKG) inhibitor. In inside-out patch, TMP activated BK_(Ca) channels by increasing open-state probability (N_(Po)) and decreasing close time (Tc) in a concentration-dependent manner. TMP (0.73--8.07 mmol/L) in the bath solution increased N_(Po) from (0.01±0.003) to (0.03±0.01)--(1.21±0.18) (P<0.01, n=10)，and decreased Tc from (732.33±90.67) ms to (359.67±41.30)--(2.96±0.52) ms (P<0.01, n=10). These actions of TMP occurred even when the free Ca~(2+) concentration in the bath was reduced to -- 0 mmol/L. The specific inhibitors of PKA (H-89, 3 #mu#mol/L) and PKG (KT-5823, 1 #mu#mol/L) had no influence on the activation of TMP on BK_(Ca) channels. These findings suggest that TMP can directly activate BK_(Ca) channels in coronary artery smooth muscle, which probably is an important mechanism in dilating coronary artery.

Key words: Tetramethylpyrazine;Large-conductance Ca~(2+)-activated potassium channels;Porcine coronary smooth muscle cells;Patch-clamp techniques

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引用本文：

杨艳艳, 曾晓荣, 刘智飞, 蔡芳, 李妙龄, 周文, 裴杰. 川芎嗪对猪冠状动脉平滑肌细胞大电导钙激活钾通道的作用[J]. 生理学报 2006; 58 (1): .

Yang Yanyan, Zeng Xiaorong, Liu Zhifei, Cai Fang, Li Miaoling, Zhou Wen, Pei Jie. Effects of tetramethylpyrazine on large--conductance Ca~(2+)--activated potassium channels in porcine coronary artery smooth muscle cells. Acta Physiol Sin 2006; 58 (1): (in Chinese with English abstract).