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Annu Rev Physiol. 2010;72:395-412. doi: 10.1146/annurev-physiol-021909-135725.

The physiological significance of the cardiotonic steroid/ouabain-binding site of the Na,K-ATPase.

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1
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0524, USA. jerry.lingrel@uc.edu

Abstract

The Na,K-ATPase is the membrane "pump" that generates the Na(+) and K(+) gradients across the plasma membrane that drives many physiological processes. This enzyme is highly sensitive to inhibition by cardiotonic steroids, most notably the digitalis/ouabain class of compounds, which have been used for centuries to treat congestive heart failure and arrhythmias. The amino acids that constitute the ouabain-binding site are highly conserved across the evolutionary spectrum. This could be fortuitous or could result from this site being conserved because it has an important biological function. New physiological approaches using genetically engineered mice are being used to define the biological significance of the "receptor function" of the Na,K-ATPase and its regulation by potential endogenous cardiotonic steroid-like compounds. These studies extend the reach of earlier studies involving the biochemical purification of endogenous regulatory ligands.

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