Epithelial Na+,K+-ATPase — A Sticky Pump

Abstract

Na+,K+-ATPase is an ATP-powered ion pump that establishes concentration gradients for Na+ and K+ ions across the plasma membrane in all animal cells by pumping Na+ from the cytoplasm and K+ from the extracellular medium. This heterodimeric enzyme, a member of P-type ATPases, is composed of a catalytic α-subunit with ten transmembrane do‐ mains and a heavily glycosylated auxiliary β-subunit. The Na+,K+-ATPase is specifically inhibited by cardiotonic steroids like ouabain, which bind to the enzyme’s α-subunit from the extracellular side and thereby block the ion pumping cycle. Na+,K+-ATPAse gen‐ erates ion gradients that establishes the driving force for the transepithelial transport of several solutes and nutrients. The effectiveness of this vectorial transport motivated by Na+,K+-ATPase depends on the integrity of epithelial junctions that are essential for the maintenance of the polarized localization of membrane transporters, including the lateral sodium pump. This chapter reviews the facts showing that, in addition to pumping ions, the Na+,K+-ATPase located at the cell borders functions as a cell adhesion molecule and discusses the role of the Na+,K+-ATPase β-subunit in establishing and maintaining cell– cell interactions. Furthermore, Na+,K+-ATPase is a multifunctional protein that, in addi‐ tion to pumping ions asymmetrically and participating in cell–cell contacts, acts as specif‐ ic receptor for the hormone ouabain and transduces extracellular signals. Thus, when bearing in mind with transporting epithelia phenotype, the importance of modulation of cell contacts by Na+,K+-ATPase can hardly be underestimated.