Document Detail

Fatty acid ethyl esters, nonoxidative metabolites of ethanol, accelerate the kinetics of activation of the human brain delayed rectifier K+ channel, Kv1.1.
MedLine Citation:
PMID:  8955075     Owner:  NLM     Status:  MEDLINE    
Herein we demonstrate that the major metabolites of ethanol in neural tissues, fatty acid ethyl esters, dramatically accelerate the kinetics of the voltage-induced activation of the human brain delayed rectifier potassium channel, Kv1.1. Specifically, the external application of ethyl oleate (20 microM) to Sf9 cells expressing the recombinant Kv1.1 channel resulted in a decrease in the rise times of the macroscopic current (e.g. from 51.7 +/- 13.1 to 12.8 +/- 3.0 ms at 0 mV for 10-90% rise times) and a 10-mV hyperpolarizing shift (at 0 mV) in the voltage dependence of channel activation. These effects were dose-dependent (half-maximal effect at 7 microM), saturable and specific (i.e. fatty acid methyl esters were without effect). Although application of either ethanol or oleic acid alone did not result in alterations of the activation kinetics, the concomitant application of ethanol and oleic acid reproduced the effects of fatty acid ethyl esters with a temporal course which paralleled the intracellular accumulation of fatty acid ethyl esters in Sf9 cells. Moreover, application of fatty acid ethyl esters (but not ethanol) to rat hippocampal cells in culture produced similar effects on hippocampal delayed rectifier currents. Collectively, these results demonstrate that pathophysiologically relevant concentrations of metabolites of ethanol, fatty acid ethyl esters, modulate the function of a prototypic neuronal ion channel and thus likely contribute to the pathophysiologic sequelae of ethanol abuse in excitable tissues.
R A Gubitosi-Klug; R W Gross
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  271     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1996 Dec 
Date Detail:
Created Date:  1997-01-23     Completed Date:  1997-01-23     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  32519-22     Citation Subset:  IM    
Division of Bioorganic Chemistry and Molecular Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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MeSH Terms
Electric Conductivity
Esters / pharmacology*
Ethanol / chemistry,  pharmacology
Fatty Acids / metabolism
Hippocampus / physiology*
Ion Channel Gating
Membrane Potentials
Potassium Channels / drug effects,  physiology*
Recombinant Proteins
Reg. No./Substance:
0/Esters; 0/Fatty Acids; 0/Potassium Channels; 0/Recombinant Proteins; 64-17-5/Ethanol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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