Issue Archive

[Angiotensin II activates large-conductance Ca2+-activated potassium channels in human mesenteric artery smooth muscle cells.] [Article in Chinese]

WEN Jing, CHENG Jun, LI Pengyun, MAO Liang, YUE Xiaolan, , LI Chang, YANG Yan^*

Department of Electrophysiology, Institute of Cardiovasology, State Key Laboratory, Luzhou Medical College, Luzhou 646000, China

Abstract

The aim of present study was to explore the vasodilatation mechanism of angiotensin II (AngII) at the molecular level by investigating the effect of AngII on large-conductance Ca(2+)-activated potassium channels (BK(Ca)) in human mesenteric artery smooth muscle cells. The effect of AngII on BK(Ca) was observed by using patch clamp single channel recording technique and amphotericin-perforated whole-cell recording technique. AngII type 1 receptor (AT(1)R) and AngII type 2 receptor (AT(2)R) mRNA expression in human mesenteric artery was detected by RT-PCR. In cell-attached patch (Vm = +40 mV), AngII (100 nmol/L) had no significant effect on BK(Ca). After pretreatment with Valsartan (a specific inhibitor of AT(1)R, 10 μmol/L), 25, 100 and 250 nmol/L AngII stimulated BK(Ca) activity significantly in a dose response manner. After pretreatment of Valsartan, AngII (100 nmol/L) enhanced BK(Ca) open probability (NP(O)) from 0.010 ± 0.003 to 0.039 ± 0.015, decreased the mean close time (T(C)) of BK(Ca) markedly from (2 729.5 ± 808.6) ms to (487.7 ± 182.5) ms (n = 11, P < 0.05) , but AngII had no significant influences on the amplitude (Amp) and the mean open time (T(O)) of BK(Ca). Further PD123,319 (a specific inhibitor of AT(2)R) treatment prevented the stimulatory effect of AngII: PD123,319 decreased the NP(O) of BK(Ca) from 0.016 ± 0.003 to 0.004 ± 0.001 (n = 5, P < 0.05), but had no significant influences on Amp, T(O) and T(C) of BK(Ca). In addition, after pretreatment with Valsartan and PD123,319, AngII (100 nmol/L) had no significant effect on BK(Ca). In the amphotericin-perforated whole-cell patch-clamp configuration, after pretreatment with Valsartan, the current density of BK(Ca) at the voltage of -60 - +30 mV had no significant changes before and after adding 100 nmol/L AngII, but the current density of BK(Ca) at the voltage of +40 mV, +50 mV and +60 mV increased significantly after adding 100 nmol/L AngII, from (9.03 ± 2.23) pA/pF, (12.88 ± 2.55) pA/pF and (17.26 ± 2.84) pA/pF to (12.47 ± 2.22) pA/pF, (18.71 ± 2.51) pA/pF and (27.21 ± 3.12) pA/pF (n = 6, P < 0.05), respectively. Using RT-PCR, the AT(1)R mRNA and AT(2)R mRNA from isolated human mesenteric artery were detected. So we can draw a conclusion, AngII can stimulate BK(Ca) activity in human mesenteric artery smooth muscle cells after pretreatment with Valsartan, which is possibly mediated by AT(2)R.

Key words: Angiotensin II; angiotensin II type 2 receptor; large conductance calcium-activated potassium channel; human mesenteric artery

Received: 2012-05-22　　Accepted: 2012-09-28

Corresponding author: 杨艳　　E-mail: wyangyan@yahoo.com.cn

Citing This Article：

WEN Jing, CHENG Jun, LI Pengyun, MAO Liang, YUE Xiaolan, , LI Chang, YANG Yan. [Angiotensin II activates large-conductance Ca2+-activated potassium channels in human mesenteric artery smooth muscle cells.] [Article in Chinese]. Acta Physiol Sin 2013; 65 (1): 39-46 (in Chinese with English abstract).