Regulation of Na,K-ATPase by endogenous ouabain-like materials

Sodium, potassium-ATPase (NKA) is an essential energy transduction mechanism in which the free energy released by hydrolysis of ATP is transferred to an electrochemical gradient across the cell membrane. The asymmetry of sodium in this gradient is coupled to membrane transport mechanisms which affect transmembrane movement of a range of solutes and electrolytes. Recent advances in the molecular biology of NKA have revealed important new aspects of structure-function relationships as well as illuminating the basis for variations in cardiac glycoside sensitivity of the enzyme. The search for endogenous mammalian counterparts of the cardiac glycosides, which regulate the activity of the enzyme by interacting from the extracellular surface at this receptor site, has moved ahead dramatically with evidence that ouabain is an endogenous product of the mammalian adrenal cortex. These advances, and problems raised by them, are explored in this review.