Potent inhibition of the aortic smooth muscle maxi-K channel by clinical doses of ethanol |
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Authors: | Walters F S Covarrubias M Ellingson J S |
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Affiliation: | Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. |
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Abstract: | We investigated the effects ofclinically relevant ethanol concentrations (5-20 mM) on thesingle-channel kinetics of bovine aortic smooth muscle maxi-K channelsreconstituted in lipid bilayers (1:1palmitoyl-oleoyl-phosphatidylethanolamine:palmitoyl-oleoyl-phosphatidylcholine). Ethanol at 10 and 20 mMdecreased the channel open probability (Po) by75 ± 20.3% mainly by increasing the mean closed time (+82 to+960%, n = 7). In some instances, ethanol alsodecreased the mean open time (40.8 ± 22.5%). ThePo-voltage relation in the presence of 20 mMethanol exhibited a rightward shift in the midpoint of voltageactivation (V1/2 17 mV), a slightlysteeper relationship (change in slope factor, k, 2.5 mV), and a decreased maximum Po (from~0.82 to ~0.47). Interestingly, channels inhibited by ethanol atlow Ca2+ concentrations (2.5 µM) were veryresistant to ethanol in the presence of increased Ca2+ ( 20 µM). Alcohol consumption in clinically relevant amounts may alterthe contribution of maxi-K channels to the regulation of arterial tone. |
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