Electrophysiological actions of acetate, a metabolite of ethanol, on hippocampal dentate granule neurons: interactions with adenosine.
Acetate is the primary breakdown product of ethanol metabolism in the liver and has been found in the brain following ethanol ingestion in rats. Systemically administered acetate has been shown to cause motor impairment, an effect which is blocked by the adenosine receptor blocker, 8-phenyltheophylline (8-PT). The effects of sodium acetate were investigated in this study using intracellular recording techniques in rat hippocampal dentate granule cells, and were compared to the actions of ethanol and adenosine individually and in conjunction with 8-PT. Acetate hyperpolarized the membrane at 0.4-0.8 mM. The amplitude and duration of the postspike train afterhyperpolarization (AHP) were increased by acetate when the cell was repolarized to the control resting membrane potential. Comparable results were seen in voltage clamp. Acetate also decreased spike frequency adaptation. The effects of acetate were mimicked by adenosine (50 microM) and ethanol (20 mM). The ethanol effects occluded those produced by acetate. All of the effects of acetate, adenosine and ethanol could be inhibited with prior perfusion of 8-PT (1-10 microM). These data suggest that the actions of the major metabolite of ethanol, acetate, may be mediated by adenosine receptor activation.
Cullen
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Department of Physiology, University of Toronto, Ont. Canada.
Carlen
P L
PL
D000085:Acetates / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D000431:Ethanol / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D000085:Acetates; D011983:Receptors, Purinergic; D000431:Ethanol; D011189:Potassium Chloride; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine