University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Psychiatry, Brudnick Neuropsychiatric Research Institute; Martin Lab

Publication Date


Document Type



Biochemistry, Biophysics, and Structural Biology | Cellular and Molecular Physiology | Neuroscience and Neurobiology


In most tissues, the function of Ca(2+)- and voltage-gated K(+) (BK) channels is modified in response to ethanol concentrations reached in human blood during alcohol intoxication. In general, modification of BK current from ethanol-naive preparations in response to brief ethanol exposure results from changes in channel open probability without modification of unitary conductance or change in BK protein levels in the membrane. Protracted and/or repeated ethanol exposure, however, may evoke changes in BK expression. The final ethanol effect on BK open probability leading to either BK current potentiation or BK current reduction is determined by an orchestration of molecular factors, including levels of activating ligand (Ca(2+) i), BK subunit composition and post-translational modifications, and the channel's lipid microenvironment. These factors seem to allosterically regulate a direct interaction between ethanol and a recognition pocket of discrete dimensions recently mapped to the channel-forming (slo1) subunit. Type of ethanol exposure also plays a role in the final BK response to the drug: in several central nervous system regions (e.g., striatum, primary sensory neurons, and supraoptic nucleus), acute exposure to ethanol reduces neuronal excitability by enhancing BK activity. In contrast, protracted or repetitive ethanol administration may alter BK subunit composition and membrane expression, rendering the BK complex insensitive to further ethanol exposure. In neurohypophyseal axon terminals, ethanol potentiation of BK channel activity leads to a reduction in neuropeptide release. In vascular smooth muscle, however, ethanol inhibition of BK current leads to cell contraction and vascular constriction.


BK beta subunits, alcohol tolerance, ethanol-recognition site, ion channels, membrane lipids, n-alkanols, slo1 proteins

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Copyright © 2014 Dopico, Bukiya and Martin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version



Front Physiol. 2014 Dec 2;5:466. doi: 10.3389/fphys.2014.00466. eCollection 2014. Link to article on publisher's site

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Link to Article in PubMed

Journal/Book/Conference Title

Frontiers in physiology

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.



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