Tyrosine 450 in the Voltage- and Calcium-Gated Potassium Channel of Large Conductance Channel Pore-Forming (slo1) Subunit Mediates Cholesterol Protection against Alcohol-Induced Constriction of Cerebral Arteries.

ABSTRACT: Alcohol (ethanol) at physiologically relevant concentrations (<100 mM) constricts cerebral arteries via inhibition of voltage- and calcium-gated potassium channels of large conductance (BK) located in vascular smooth muscle (VSM). These channels consist of channel-forming slo1 (cbv1, KCNMA1) and accessory beta1 (KCNMB1) subunits. An increase in VSM cholesterol (CLR) via either dietary CLR intake or in vitro CLR enrichment was shown to protect against endothelium-independent, alcohol-induced constriction of cerebral arteries. The molecular mechanism(s) of this protection remains unknown. Here, we demonstrate that CLR enrichment of de-endothelialized middle cerebral arteries (MCAs) of rat increased CLR content in the VSM in a concentration-dependent manner. CLR enrichment blunt

SUBMITTER: North K 

PROVIDER: S-EPMC6170972 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature