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

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• 作者：Anna N. Bukiya ; Jianxi Liu ; Alej ; ro M. Dopico
• 关键词：Channel auxiliary subunit ; MaxiK channel ; Cerebral artery ; Alcohol ; Vasoconstriction ; KCNMB1
• 刊名：FEBS Letters
• 出版年：2009
• 出版时间：3 September 2009
• 年：2009
• 卷：583
• 期：17
• 页码：2779-2784
• 全文大小：359 K

文摘

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