Augmentation of ouabain sensitivity of rat liver Na/K‐ATPase by in vivo adenovirus‐mediated expression of the Na/K‐ATPase α2 subunit

These are the first experiments to study the effect of in vivo expression of the Na/K-ATPase alpha2 subunit which serves as a receptor for cardiac glycosides. The alpha2 subunit is not normally expressed in rat liver, so hepatocytes which lack endogenous alpha2 protein are a logical first target to study the effects of alpha2 expression on membrane Na/K-ATPase activity. At 3 days after alpha2 adenovirus vector infusion, Wistar rat livers contained alpha2 DNA, alpha2 mRNA, and alpha2 protein. Rat liver membrane ouabain binding activity and the sensitivity of Na/K-ATPase activity to ouabain significantly increased. Total membrane Na/K-ATPase was regulated at a constant level while expressed alpha2 activity represented 10% of the total active Na/K-ATPase sites in alpha2 transduced rat liver. These studies are the first to establish a paradigm in which an endogenous drug receptor is expressed to alter cellular pharmacologic sensitivity.