Isozymes of the na,k-atpase: heterogeneity in structure, diversity
in function.
Blanco, Gustavo, and Robert W. Mercer.
Department of Cell Biology and Physiology, Washington University
School of Medicine, St. Louis, MO 63110, USA.
APStracts 5:0113F, 1998.
The Na,K-ATPase is characterized by a complex molecular heterogeneity
that results from the expression and differential association of
multiple 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 tissue specific and developmental
pattern of expression suggests that the different Na,K-ATPases have
evolved distinct properties to respond to cellular requirements. This
article focuses on the functional properties, regulation and possible
physiological relevance of the Na pump isozymes. The coexistence of
multiple [alpha] and [beta] isoforms in most cells has hindered the
understanding of the roles of the individual polypeptides. The use of
heterologous expression systems has helped circumvent this problem.
The kinetic characteristics of different Na,K-ATPase isozymes to the
activating cations (Na+ and K+), the substrate ATP and the inhibitors
Ca2+ and ouabain, demonstrates that each isoform has distinct
properties. In addition, intracellular messengers differentially
regulate the activity of the individual Na,K-ATPase isozymes. Thus,
the regulation of specific Na pump isozymes gives cells the ability
to precisely coordinate Na,K-ATPase activity to their physiological
requirements.
Received 11 November 1997; accepted in final form 18 June 1998.
APS Manuscript Number F353-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 30 July 1998