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 Cai2+ lower and higher than ∼15 μM, respectively. By increasing cbv1’s apparent Cai2+-sensitivity, accessory BK β1 subunits shift the activation-to-inhibition crossover of EtOH action to <3 μM Cai2+, 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 β1 is the molecular effector of alcohol-induced BK current inhibition and cerebrovascular constriction.