Alcohol stimulates Na+/Ca2+ exchange in brain mitochondria.
Ethanol, at low concentrations, specifically stimulates the Na(+)-dependent Ca2(+)-efflux in brain mitochondria. In addition, at higher concentrations, ethanol inhibits the Na(+)-independent Ca2(+)-efflux. The electrogenic Ca(+)-uptake system is not affected by ethanol. The specific stimulation of Na+/Ca2+ exchange reaches a maximum of 60% stimulation, with half-maximal stimulation at 130 mM ethanol. The inhibition of the Na(+)-independent efflux is proportional to the ethanol concentration, becoming significant only above 200 mM, with 50% inhibition at 0.5 M. The inhibition of the Na(+)-independent efflux is, in large part, due to an inhibition of the activation of the Cyclosporin-sensitive pore. Long-term ethanol-feeding had no effect on the Ca2+ transport systems and their sensitivity to acute ethanol treatment. It is suggested that the stimulation of the Na(+)-dependent Ca2(+)-efflux, which is the dominant Ca2+ efflux pathway in brain mitochondria, contributes to the intoxicating effects of ethanol.
Rottenberg
H
H
Pathology Department, Hahnemann University, Philadelphia, PA 19102.
Marbach
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D015220:Calcium Channels; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003524:Cyclosporins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger; D013268:Stimulation, Chemical
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D003524:Cyclosporins; D019831:Sodium-Calcium Exchanger; C034703:mitochondrial calcium uniporter; D000431:Ethanol; D012964:Sodium; D002118:Calcium