The BK channel accessory β1 subunit determines alcohol-induced cerebrovascular constriction

被引：53

作者：

Bukiya, Anna N. ^{[1
]}

Liu, Jianxi ^{[1
]}

Dopico, Alejandro M. ^{[1
]}

机构：

[1] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Pharmacol, Memphis, TN 38163 USA

来源：

FEBS LETTERS | 2009年 / 583卷 / 17期

关键词：

Channel auxiliary subunit; MaxiK channel; Cerebral artery; Alcohol; Vasoconstriction; KCNMB1; CA2+-ACTIVATED K+-CHANNELS; ARTERY SMOOTH-MUSCLE; LARGE-CONDUCTANCE; POTASSIUM CHANNELS; ETHANOL INCREASES; BETA-1; SUBUNIT; CALCIUM; CA2+; ACTIVATION; SPARKS;

D O I：

10.1016/j.febslet.2009.07.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2779 / 2784

页数：6

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