The present invention shows that site-specific antibodies to the (Na++K+)-ATPase exert a potent biological effect in cardiac myocytes and demonstrates a key structural region of the enzyme that participates in the regulation of cardiac contractility. These results establish an important link between a biological action and a precise molecular structure of the (Na++K+)-ATPase. Furthermore, the antibody-induced positive inotropic effect is independent of inactivation of the enzyme may reveal a novel mode for (Na++K+)-ATPase to regulate cardiac function. The data provide new molecular insights into the structural and functional relationship of the ubiquitous (Na++K+)-ATPase.