Ethanol and (Na+,K+)-ATPase: alteration of Na(+)-K+ selectivity

Relative internal concentrations of Na+ and K+ are important in regulating (Na+,K+)-ATPase in situ. Ethanol is known to inhibit (Na+,K+)-ATPase and to reduce K+ affinity, but the concentrations required for these effects in vitro are large compared with those probably attainable in vivo. Yet, there is evidence suggesting that ethanol has physiologically relevant effects on (Na+,K+)-ATPase. We have investigated the effects of ethanol on selectivity for Na+ versus K+. At 150 mM, ethanol had little effect on (Na+,K+)-ATPase activity under the usual assay conditions, slightly (but nonsignificantly) reduced K+ affinity, and had no effect on extrapolated Na+ affinity in the absence of K+. However, ethanol had marked effects on cation selectivity, doubling the Ki for K+ on Na+ affinity and halving the Ki for Na+ on K+ affinity. These data show that ethanol, at concentrations too small for effects on (Na+,K+)-ATPase activity under optimal assay conditions, can alter its responses to changes in Na+ or K+.