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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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Citing This Article：

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).