ISOZYMES OF THE NA-K-ATPASE - HETEROGENEITY IN STRUCTURE, DIVERSITY IN FUNCTION

The Na-K-ATPase is characterized by a complex molecular heterogeneity that results from the expression and differential association of multi ple isoforms of both its alpha- and beta-subunits. At present, as many as four different alpha-polypeptides (alpha 1, alpha 2, alpha 3, and alpha 4) and three distinct beta-isoforms (beta 1, beta 2, and beta 3) have been identified in mammalian cells. The stringent constraints on the structure of the Na pump isozymes during evolution and their tiss ue-specific and developmental pattern of expression suggests that the different Na-K-ATPases have evolved distinct properties to respond to cellular requirements. This review focuses on the functional propertie s, regulation, and possible physiological relevance of the Na pump iso zymes. The coexistence of multiple alpha- and beta-isoforms in most ce lls has hindered the understanding of the roles of the individual poly peptides. The use of heterologous expression systems has helped circum vent this problem. The kinetic characteristics of different Na-K-ATPas e isozymes to the activating cations (Na+ and K+), the substrate ATP, and the inhibitors Ca2+ and ouabain demonstrate that each isoform has distinct properties. In addition, intracellular messengers differentia lly regulate the activity of the individual Na-K-ATPase isozymes. Thus the regulation of specific Na pump isozymes gives cells the ability t o precisely coordinate Na-K-ATPase activity to their physiological req uirements.