© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
The Na, K-ATPase in the failing human heart
aLaboratory of Muscle Research and Molecular Cardiology, Clinic III of Internal Medicine, University of Cologne, Joseph-Stelzmann-Strasse 9, Cologne 50924, Germany
bMedical Department B, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
robert.schwinger{at}medizin.uni-koeln.de
* Corresponding author. Tel.: +49-221-478-6205; fax: +49-221-478-6550.
The Na, K-ATPase consists of 
- and β-subunits and actively transports Na out and K into the myocyte. It is the receptor for cardiac glycosides exerting its positive inotropic effect by inhibiting enzyme activity, decreasing the driving force for the Na/Ca-exchange and increasing cellular content and release of Ca during depolarization. The specific binding capacity for cardiac glycosides is utilized as a tool for Na, K-ATPase quantification with high accuracy and precision. In treatment of patients with heart failure cardiac glycosides improve symptoms and reduce the need for hospitalization without affecting mortality. In endomyocardial biopsies from patients with compromised cardiac function total Na, K-ATPase concentration is decreased by 
40% and a correlation between decrease in heart function and decrease in Na, K-ATPase concentration exists. At the subunit level, the 1-, 3- and β1-proteins are reduced in human heart failure. During digitalization 30% of remaining Na, K-pumps are occupied by digoxin. Thus, a total of not less than half the Na, K-pumps may be out of function in the myocardium of digitalised heart failure patients. It is still a matter of debate whether a digitalis-like factor exists. There is a pressing need for the identification of its precise chemical structure, properties and quantitative relation to the Na, K-ATPase. It is recommended that cardiac glycosides are prescribed to heart failure patients who are still having heart failure symptoms after institution of mortality reducing therapy. Cardiac glycoside treatment is still the only safe inotropic drug for oral use that improves hemodynamics in patients with compromised cardiac function.
KEYWORDS Heart failure; Intra/extracellular ions; Ion pumps
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