The BK channel accessory β1 subunit determines alcohol-induced cerebrovascular constriction
- Bukiya, Anna N.
- Liu, Jianxi
- Dopico, Alejandro M.
DOIAbstract
AbstractEthanol-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 ∼15μM, respectively. By increasing cbv1’s apparent Cai2+-sensitivity, accessory BK β1 subunits shift the activation-to-inhibition crossover of EtOH action to <3μM 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 β...