Invited Review CALL FOR PAPERS Molecular Mechanisms Linking Salt to Hypertension Physiological role of the 1- and 2-isoforms of the Na -K -ATPase and biological significance of their cardiac glycoside binding site
نویسندگان
چکیده
Iva Dostanic-Larson, John N. Lorenz, James W. Van Huysse, Jon C. Neumann, Amy E. Moseley, and Jerry B Lingrel Departments of Molecular Genetics, Biochemistry and Microbiology, and Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, Cincinnati, Ohio; University of Ottawa Heart Institute, Hypertension Unit, Ottawa; and Departments of Medicine and Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
منابع مشابه
The sodium pump and hypertension: a physiological role for the cardiac glycoside binding site of the Na,K-ATPase.
T he Na,K-ATPase (or Na pump) is an integral membrane protein that transports Na and K across the plasma membrane of almost all animal cells and couples this work to the hydrolysis of the terminal phosphate bond of ATP (1). A significant fraction (up to 30%) of the ATP generated by cell metabolism is dedicated to this active transport process. The electrical gradient created by the Na pump is e...
متن کاملThe highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation.
The Na,K-ATPase contains a binding site for cardiac glycosides, such as ouabain, digoxin, and digitoxin, which is highly conserved among species ranging from Drosophila to humans. Although advantage has been taken of this site to treat congestive heart failure with drugs such as digoxin, it is unknown whether this site has a natural function in vivo. Here we show that this site plays an importa...
متن کاملThe cardiac glycoside binding site on the Na,K-ATPase alpha2 isoform plays a role in the dynamic regulation of active transport in skeletal muscle.
The physiological significance of the cardiac glycoside-binding site on the Na,K-ATPase remains incompletely understood. This study used a gene-targeted mouse (alpha2(R/R)) which expresses a ouabain-insensitive alpha2 isoform of the Na,K-ATPase to investigate whether the cardiac glycoside-binding site plays any physiological role in active Na(+)/K(+) transport in skeletal muscles or in exercise...
متن کاملSelectivity of digitalis glycosides for isoforms of human Na,K-ATPase.
There are four isoforms of the alpha subunit (alpha1-4) and three isoforms of the beta subunit (beta1-3) of Na,K-ATPase, with distinct tissue-specific distribution and physiological functions. alpha2 is thought to play a key role in cardiac and smooth muscle contraction and be an important target of cardiac glycosides. An alpha2-selective cardiac glycoside could provide important insights into ...
متن کاملNew Molecular Determinants Controlling the Accessibility of Ouabain to Its Binding Site in Human Na,K-ATPase Isoforms
Inhibition of Na,K-ATPase 2 isoforms in the human heart is supposed to be involved in the inotropic effect of cardiac glycosides, whereas inhibition of 1 isoforms may be responsible for their toxic effects. Human Na,K-ATPase 1 and 2 isoforms exhibit a high ouabain affinity but significantly differ in the ouabain association and dissociation rates. To identify the structural determinants that ar...
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