Potent inhibition of the aortic smooth muscle maxi-K channel by clinical doses of ethanol.
We investigated the effects of clinically relevant ethanol concentrations (5-20 mM) on the single-channel kinetics of bovine aortic smooth muscle maxi-K channels reconstituted in lipid bilayers (1:1 palmitoyl-oleoyl-phosphatidylethanolamine: palmitoyl-oleoyl-phosphatidylcholine). Ethanol at 10 and 20 mM decreased the channel open probability (P(o)) by 75 +/- 20.3% mainly by increasing the mean closed time (+82 to +960%, n = 7). In some instances, ethanol also decreased the mean open time (-40.8 +/- 22. 5%). The P(o)-voltage relation in the presence of 20 mM ethanol exhibited a rightward shift in the midpoint of voltage activation (DeltaV(1/2) congruent with 17 mV), a slightly steeper relationship (change in slope factor, Deltak, congruent with -2.5 mV), and a decreased maximum P(o) (from approximately 0.82 to approximately 0. 47). Interestingly, channels inhibited by ethanol at low Ca(2+) concentrations (2.5 microM) were very resistant to ethanol in the presence of increased Ca(2+) (>/= 20 microM). Alcohol consumption in clinically relevant amounts may alter the contribution of maxi-K channels to the regulation of arterial tone.
Walters
F S
FS
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Covarrubias
M
M
Ellingson
J S
JS
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D002492:Central Nervous System Depressants / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008051:Lipid Bilayers / Q000737:chemistry; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010539:Permeability / Q000187:drug effects; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated
D002492:Central Nervous System Depressants; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; D000431:Ethanol; D002118:Calcium; C028694:1-palmitoyl-2-oleoylphosphatidylcholine