For decades, the Na/K-ATPase has been proposed and recognized as one of the targets for the regulation of renal salt handling. While direct inhibition of the Na/K-ATPase ion transport activity and sodium reabsorption was the focus, the underlying mechanism is not well understood since decreases in basolateral Na/K-ATPase activity alone do not appear sufficient to decrease net sodium reabsorption across the renal tubular epithelium. The newly appreciated signaling function of Na/K-ATPase, which can be regulated by Na/K-ATPase ligands (cardiotonic steroids (CTS)) and reactive oxygen species (ROS), has been widely confirmed and provides a mechanistic framework for natriuresis regulation in renal proximal tubule (RPT). The focus of this review aims to understand, in renal proximal tubule, how the activation of Na/K-ATPase signaling function, either by CTS or ROS, stimulates a coordinated reduction of cell surface Na/K-ATPase and sodium/hydrogen exchanger isoform 3 (NHE3) that leads to ultimately decreases in net transcellular sodium transport/reabsorption.
Part of the book: Biomarkers and Bioanalysis Overview