Effects of in vitro ethanol on the brain cation pump in alcoholics and controls

In vivo ethanol exposure reduces in vitro Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) sensitivity to ethanol in some animal models, but very little is known about the effects of ethanol on human brain Na+,K(+)-ATPase. Cerebral cortex homogenates from 13 male alcoholic and 9 control subjects were assayed for K(+)-p-nitrophenylphosphatase (K(+)-pNPPase, a measure of Na+,K(+)-ATPase) and Mg(2+)-pNPPase activities at 37 degrees for 20 min in 75 mM imidazole-HCl (pH 7.4), 5 mM p-nitrophenylphosphate, 5 mM MgCl2, and 20 mM KCl, with or without 1 mM ouabain. Native K(+)-pNPPase activites were similar in control and alcoholic brains (61.5 +/- 3.5 vs 55.3 +/- 3.1 nmol/mg/min). In vitro exposure to a near lethal ethanol level (0.5%, or 110 mM) was without effect, whereas 5% ethanol inhibited K(+)-pNPPase activity by about 28% (P < 0.001) in both groups. Both 0.5 and 5% ethanol in vitro significantly stimulated Mg(2+)-pNPPase activity (1-2% and 19-20%, respectively). By comparison, mouse brain K(+)-pNPPase was inhibited significantly by in vitro ethanol, and Mg(2+)-pNPPase activity was unaffected. Ethanol levels attainable in humans may not be sufficient to alter significantly brain Na+,K(+)-ATPase activity.