Inward Rectifier Potassium Channels in the Basilar Artery During Chronic Alcohol Consumption

Abstract

The goals of this study were to determine whether chronic alcohol consumption alters potassium channel-mediated reactivity in the basilar artery and to determine a potential mechanism that might account for the effects of alcohol on the basilar artery. Sprague-Dawley rats were fed liquid diets with or without alcohol for 2 to 3 months. We measured diameter of the basilar artery in response to potassium channel inhibitors and activators. Protein level of inward rectifier potassium channel subunit Kir2.1 in the basilar artery was determined by Western blot. Topical application of glibenclamide (1 and 10 microM) significantly constricted the basilar artery at high dose; iberiotoxin (10 and 100 nM), 4-AP (0.1 and 1 mM), and BaCl2 (1 and 10 microM) produced dose-related constriction in both non-alcohol-fed and alcohol-fed rats. However, the magnitude of constriction in response to BaCl2 was significantly less in alcohol-fed rats compared with non-alcohol-fed rats. Topical application of KCl (1 and 3 mM), cromakalim (0.1 and 0.3 microM), and NS1619 (10 and 30 microM) induced dose-related dilation in non-alcohol-fed and alcohol-fed rats. However, the magnitude of vasodilation in response to KCl was significantly less in alcohol-fed rats compared with non-alcohol-fed rats. In addition, Kir2.1 protein level in the basilar artery was significantly reduced in alcohol-fed compared with non-alcohol-fed rats. These findings suggest that chronic alcohol consumption reduces expression of inward rectifier potassium channels and inhibits KIR channel-mediated dilation in the basilar artery.