Bukiya Anna N, Liu Jianxi, Dopico Alejandro M
The University of Tennessee Health Science Center, College of Medicine, Department of Pharmacology, Memphis, TN 38163, USA.
FEBS Lett. 2009 Sep 3;583(17):2779-84. doi: 10.1016/j.febslet.2009.07.019. Epub 2009 Jul 17.
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.
乙醇诱导的心肌细胞大电导、钙和电压门控钾（BK）电流抑制会导致脑血管收缩，但介导乙醇作用的分子靶点仍不清楚。利用脑动脉心肌细胞的BK通道形成（cbv1）亚基，我们证明乙醇分别在细胞内钙离子（Ca(i)(2+)）低于和高于约15微摩尔时增强和抑制电流。通过增加cbv1明显的Ca(i)(2+)敏感性，辅助BKβ(1)亚基将乙醇作用的激活到抑制交叉点转移到<3微摩尔Ca(i)(2+)，从而在心肌细胞收缩期间发现的条件下抑制电流。敲低KCNMB1可抑制乙醇对动脉心肌细胞BK电流和血管直径的降低。因此，BKβ(1)是酒精诱导的BK电流抑制和脑血管收缩的分子效应器。
