The BK channel accessory β1 subunit determines alcohol-induced cerebrovascular constriction
The BK channel accessory β1 subunit determines alcohol-induced cerebrovascular constriction
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DOI：
10.1016/j.febslet.2009.07.019
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发表时间：
2009-09-03
期刊：
影响因子：
3.5
通讯作者：
Dopico, Alejandro M.
中科院分区：
文献类型：
--
作者：
Bukiya, Anna N.;Liu, Jianxi;Dopico, Alejandro M.
乙醇诱导的心肌细胞大电导、钙和电压门控钾（BK）电流的抑制导致脑血管收缩，但介导EtOH作用的分子靶点尚不清楚。利用脑动脉肌细胞的BK通道形成（cbv1）亚基，我们证明了EtOH分别在Ca-i（2+）低于15 μ M和高于15 μ M时增强和抑制电流。通过增加cbv1对Ca-i（2+）的表观敏感性，辅助BK β(1)亚基将EtOH作用的激活-抑制交叉转移到< 3 μ M Ca-i(2+)，从而在肌细胞收缩过程中抑制电流。敲低KCNMB1可抑制动脉肌细胞BK电流和血管直径的etoh降低。因此，BK β(1)是酒精诱导的BK电流抑制和脑血管收缩的分子效应物。(C) 2009年欧洲生化学会联合会。Elsevier b.v.版权所有。
Ethanol-induced inhibition of myocyte large conductance, calcium- and voltage-gated potassium (BK) current causes cerebrovascular constriction, yet the molecular targets mediating EtOH action remain unknown. Using BK channel-forming (cbv1) subunits from cerebral artery myocytes, we demonstrate that EtOH potentiates and inhibits current at Ca-i(2+) lower and higher than similar to 15 mu M, respectively. By increasing cbv1's apparent Ca-i(2+)-sensitivity, accessory BK beta(1) subunits shift the activation-to-inhibition crossover of EtOH action to < 3 mu M Ca-i(2+), with consequent inhibition of current under conditions found during myocyte contraction. Knocking-down KCNMB1 suppresses EtOH-reduction of arterial myocyte BK current and vessel diameter. Therefore, BK beta(1) is the molecular effector of alcohol-induced BK current inhibition and cerebrovascular constriction. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.