Na,K-ATPase Subunit Heterogeneity as a Mechanism for Tissue-Specific Ion Regulation

The Na,K-ATPase comprises a family of isozymes that catalyze the active transport of cytoplasmic Na+ for extracellular K+ at the plasma membrane of cells. Isozyme diversity for the Na,K-ATPase results from the association of different molecular forms of the α (α1, α2, α3, and α4) and β (β1, β2, and β3) subunits that constitute the enzyme. The various isozymes are characterized by unique enzymatic properties and a highly regulated pattern of expression that depends on cell type, developmental stage, and hormonal stimulation. The molecular complexity of the Na,K-ATPase goes beyond its α and β isoforms and, in certain tissues, other accessory proteins associate with the enzyme. These small membrane-bound polypeptides, known as the FXYD proteins, modulate the kinetic characteristics of the Na,K-ATPase. The experimental evidence available suggests that the molecular and functional heterogeneity of the Na,K-ATPase is a physiologically relevant event that serves the specialized functions of cells. This article focuses on the functional properties, regulation, and the biological relevance of the Na,K-ATPase isozymes as a mechanism for the tissue-specific control of Na+ and K+ homeostasis.