Molecular Pharmacology, Vol 16, 135-146, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Nature of the Transport Adenosine Triphosphatase-Digitalis Complex: XIV. Inotropy and Cardiac Glycoside Interaction with Na⁺, K⁺-ATPase of Isolated Cat Papillary Muscles

¹ Department of Cell Biophysics, Baylor College of Medicine, Houston, Texas, and Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio

A mathematical model was developed that allows the use of [³H]ouabain binding to estimate the free and occupied digitalis receptors in crude homogenates from cat right ventricular papillary muscles. Cat papillary muscles were exposed to concentrations of digoxin or ouabain that produced an inotropic effect. The fraction of occupied receptors was estimated using the model. There was a good correlation between the number of receptors occupied and the increase in contractile force achieved. When the inotropic effect was washed out, the number of occupied receptors decreased to control (zero receptors occupied). The results support the concept that the Na⁺,K⁺-ATPase-membrane system contains the pharmacological receptor for cardiac glycosides. No significant difference in the number of digitalis receptors in right and left ventricle and left atrium was detected. The density of digitalis receptors estimated per unit surface area and the number of receptors per cell in heart is much greater than estimates of receptor capacity for some other drugs.