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

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.