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FEBS Lett. 2009 Sep 3;583(17):2779-84. doi: 10.1016/j.febslet.2009.07.019. Epub 2009 Jul 17.

The BK channel accessory beta1 subunit determines alcohol-induced cerebrovascular constriction.

Author information

1
The University of Tennessee Health Science Center, College of Medicine, Department of Pharmacology, Memphis, TN 38163, USA.

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 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.

PMID:
19616547
PMCID:
PMC2769078
DOI:
10.1016/j.febslet.2009.07.019
[Indexed for MEDLINE]
Free PMC Article

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