[Effects of tetramethylpyrazine on large-conductance Ca²⁺-activated potassium channels in porcine coronary artery smooth muscle cells].
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 mumol/L) and PKG (KT-5823, 1 mumol/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.
Institute of Myocardial Electrophysiology, Luzhou Medical College, Luzhou 646000, China.
Yan-Yan
YY
Yang
Yan
Y
Yang
Xiao-Rong
XR
Zeng
Zhi-Fei
ZF
Liu
Fang
F
Cai
Miao-Ling
ML
Li
Wen
W
Zhou
Jie
J
Pei
D000818:Animals; D003331:Coronary Vessels / Q000166:cytology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000502:physiology; D011719:Pyrazines / Q000494:pharmacology*; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
D024681:Potassium Channels, Calcium-Activated; D011719:Pyrazines; D014665:Vasodilator Agents; C017953:tetramethylpyrazine