Beta-subunits are important modulators of the acute response to alcohol in human BK channels.
BACKGROUND
The BK channel (a Ca2+-activated potassium ion channel encoded by the slo gene) has been defined as a target of alcohol action in a number of preparations, possibly serving as primary mediator of intoxication in the Caenorhabditis elegans model system. However, we know little of the actions of alcohol on human BK, nor the consequences of BK subunit composition on alcohol action.


METHODS
Here, we use human embryonic kidney (HEK) cells to express various subunit combinations (hslo alpha+beta1 or beta4) of human BK, and examine the acute actions of alcohol on this channel using single channel recording techniques.


RESULTS
The human channel is potentiated by alcohol, although the presence of the beta1, and to a lesser extent, beta4-subunit, significantly reduced acute ethanol potentiation. Potentiation increased with concentration up to an asymptote, at which point potentiation decreased. The concentration of the asymptote differed according to subunit composition. The mechanism of potentiation was also subunit-dependent, with 25 mM ethanol affecting the mean open time of hSlo+beta4 channels, whereas channel open time was unaffected by the presence of beta1. The possibility that the known effect of the beta-subunit on calcium sensitivity accounts for its modulation of acute alcohol action is discussed.


CONCLUSIONS
Our data reinforce the idea that, as in other systems, BK may play a major role in alcohol's actions in humans, and highlight the potential role of channel subunit composition in the response to alcohol.
Feinberg-Zadek
Paula L
PL
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. feinberg@mit.edu
Treistman
Steven N
SN
D000435:Alcoholic Intoxication / Q000503:physiopathology; D001711:Biotransformation / Q000187:drug effects; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology
D002492:Central Nervous System Depressants; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D018999:Charybdotoxin; D000431:Ethanol