Key result
KCNMB1 knockdown suppresses ethanol-induced arterial constriction, identifying BK beta1 as the molecular effector.
The BK channel accessory β1 subunit is identified as the molecular effector mediating alcohol-induced cerebrovascular constriction.
Should not alter clinical alcohol guidance for cerebrovascular risk; leaves open BK channel roles in ethanol-induced 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 approximately 15 microM, 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 microM 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.
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Bukiya et al. (2009) studied Alcohol-induced cerebrovascular constriction. Ethanol and KCNMB1 knockdown was evaluated on BK current and vessel diameter. Knocking down KCNMB1 suppresses ethanol-induced reduction of arterial myocyte BK current and vessel diameter, identifying BK beta1 as the molecular effector of alcohol-induced constriction.
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