INCREASED HEPATIC NA,K-ATPASE ACTIVITY DURING HEPATIC REGENERATION ISASSOCIATED WITH INDUCTION OF THE BETA(1)-SUBUNIT AND EXPRESSION ON THE BILE CANALICULAR DOMAIN

Cellular and molecular mechanisms regulating the activity of the sodiu m pump or Na,K-ATPase during proliferation of hepatocytes following 70 % liver resection have not been defined. Na,K-ATPase may be regulated by synthesis of its alpha- and beta-subunits, by sorting to either the sinusoidal or apical plasma membrane domains, or by increasing membra ne lipid fluidity. This study investigated the time course of changes during hepatic regeneration for Na,K-ATPase activity, lipid compositio n and fluidity, and protein content of liver plasma membrane subfracti ons. As early as 4 h after hepatic resection, Na,K-ATPase activity was increased selectively in the bile canalicular fraction. It reached a new steady state at 12 h and remained elevated for 2 days. Although he patic regeneration was associated with a reduced cholesterol/phospholi pid molar ratio and increased fluidity, measured with two different pr obes, these changes in lipid metabolism were in the sinusoidal membran e domain. The Na,K-ATPase beta(1)-subunit, but not the alpha(1)-subuni t, was increased selectively at the bile canalicular surface as shown by immunoblotting of liver plasma membrane subfractions and the morpho logical demonstration at both the light and electron microscopic level s. Furthermore, cycloheximide blocked the rise in beta(1)-subunit mRNA levels. Since the time course for beta(1)-subunit accumulation was si milar to that for activation of Na,K-ATPase activity, this change impl icated the beta(1)-subunit in activating sodium pump activity.