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Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110
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 
- and
-subunits. At present, as many as four different -polypeptides
(1, 2, 3, and 4) and three distinct -isoforms (1,
2, and 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 review
focuses on the functional properties, regulation, and possible
physiological relevance of the Na pump isozymes. The coexistence of
multiple - and -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
demonstrate 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.
ouabain; sodium pump; protein kinases
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