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

Abstract 

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 lower and higher than ∼15μM, respectively. By increasing cbv1’s apparent -sensitivity, accessory BK β₁ subunits shift the activation-to-inhibition crossover of EtOH action to <3μM , 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.

Abbreviations: BK, large conductance, calcium- and voltage-gated potassium, N, number of channels present in the membrane patch, Po, channel open probability, STOC, Spontaneous Transient Outward Current, PSS, physiological saline solution, EtOH, ethanol

Keywords: Channel auxiliary subunit, MaxiK channel, Cerebral artery, Alcohol, Vasoconstriction, KCNMB1