Chronic ethanol and (Na+-K+)-adenosine triphosphate: apparent adaptation in cation binding and enzyme conformation

Sensitivity to ethanol, temperature dependence of apparent K+ affinity and temperature dependence of enzyme conformation of K+-p-nitrophenylphosphatase activity associated with (Na+,K+)-adenosine triphosphatase in brain membranes from rats treated chronically with liquid diets containing ethanol or isocaloric amounts of carbohydrate were compared. Three weeks' diet resulted in behavioral tolerance to ethanol. K+-p-nitrophenylphosphatase activity from tolerant rats was less sensitive than that from controls to inhibition by added ethanol, especially under conditions most favorable to ethanol inhibition. Apparent affinity for K+ was greater at all temperatures in ethanol-treated rats, and apparent delta S and delta H for K+-activation were reduced, opposite to effects of ethanol added in vitro. The amount of enzyme in the K+-sensitive conformation was greater at all temperatures in ethanol-treated rats, again opposite to effects of added ethanol. Apparent delta S and delta H of the conformational transition from E1 to E2 were reduced by ethanol treatment. These results are consistent with an apparent adaptation to chronic ethanol exposure in which membrane fluidity, at least in the neighborhood of (Na+,K+)-adenosine triphosphatase sites, is reduced, resulting in greater K+ affinity, more favorable transition to the phosphatase form of enzyme, a smaller entropy difference between native and K+-activated enzyme and reduced sensitivity to ethanol.