ABSTRACT
Sodium-potassium-adenosine triphosphatase (Na,K-ATPase; E.C.3.6.1.37), referred to as the sodium pump, is a plasma membrane-associated protein expressed in most eukaryotic cells. It belongs to a P-type ATPase family that includes Na,KATPase, H,K-ATPase, and Ca-ATPase in mammals and H-ATPase in yeast (1). Members in the P-type ATPase family share both homology in amino acid sequence and mechanism of catalytic reaction in which a covalent phosphate intermediate forms. Na,K-ATPase is currently the only known receptor for the cardiac glycosides. Digoxin is a cardiac glycoside that is used primarily in the treatment of congestive heart failure. Much evidence now also suggests that endogenous ligands structurally similar to digoxin exist and act as regulator(s) of sodium pump activity in heart and other tissues. Identification and characterization of the endogenous naturally occurring ligands specific to Na,K-ATPase may lead to discovery of new hormone-like endocrine systems, a disturbance of which may be involved in the etiology of diseases depending on sodium pump function. Therefore, understanding the sodium pump, its endogenous ligands, and their relationship to disease is of central importance. In this chapter, we review progress to date in understanding Na,K-ATPase relative to its structure and function, expression and regulation, tissue distribution, and interaction with cardiac glycosides and discuss diseases linked to aberrant Na,K-ATPase function.
