BK Channels: mediators and models for alcohol tolerance.
Enhanced acute tolerance predicts alcohol abuse. We describe work on the role of the calcium- and voltage-gated BK channel in alcohol tolerance, highlighting the lipid environment, BK protein isoform selection and auxiliary BK channel proteins. We show how ethanol, which had the reputation of a nonspecific membrane perturbant, is now being examined at realistic concentrations with cutting-edge techniques, providing novel molecular targets for therapeutic approaches to alcoholism. Addictive disorders impact our emotional, physical and financial status, and burden our healthcare system. Although alcohol is the focus of this review, it is highly probable, given the common neural and biochemical pathways used by drugs of abuse, that the findings described here will also apply to other drugs.
Treistman
Steven N
SN
Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan 00901, Puerto Rico. steven.treistman@upr.edu
Martin
Gilles E
GE
D000428:Alcohol Drinking / Q000235:genetics; D000818:Animals; D004361:Drug Tolerance / Q000235:genetics / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism; D008958:Models, Molecular; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism / Q000503:physiopathology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D008563:Membrane Lipids; D035683:MicroRNAs; D020033:Protein Isoforms; D000431:Ethanol