THE NA/K-ATPASE ENDOCYTOSIS AND SIGNALING pp. 39-65
Authors: Jiang Liu, Joseph I. Shapiro, Department of Medicine, University of Toledo College of Medicine, Toledo, Ohio
Abstract: The Na/K-ATPase was discovered as an energy transducing ion pump. A major difference between the Na/K-ATPase and other P-type ATPases is its ability to bind a group of chemicals called cardiotonic steroids (CTS). Endogenous CTS have been identified as a new class of endogenous hormones, functioning as important regulators of renal Na+ excretion and blood pressure. Na/K-ATPase is not only an ion pump, but also an important receptor that can transduce ligand-like effect of CTS on intracellular protein kinases. Significantly, the CTS-provoked kinase cascades are capable of inducing endocytosis of the apical NHE3 (Na/H exchanger isoform 3) and basolateral Na/K-ATPase in renal proximal tubular cells. Functionally, this CTS-induced coordinately regulation of Na/K-ATPase and NHE3 leads to the inhibition of sodium reabsorption in renal proximal tubules under physiological conditions, such as high salt diet. A defect in this regulation would reduce the ability of renal proximal tubular cells to excrete Na+, thus a contributor of salt-sensitive hypertension.