Abstract: 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.

Abstract: Antibodies binding to sites on the alpha-subunit of the (Na++K+)-ATPase increase cardiac contraction of both ventricular myocytes and mouse heart. In particular, antibodies binding to the RSATEEEPPNDD (SEQ ID NO: 1) or DVEDSYGQQWTYEQR (SEQ ID NO: 2) peptides (or isoforms/derivatives thereof) of the alpha-subunit of the (Na++K+)-ATPase, have been found to be highly inotropic. Both the antibodies and the peptides are important for the treatment of human heart failure and other contractile disorders.

Abstract: Antibodies binding to sites on the alpha-subunit of the (Na++K+)-ATPase increase cardiac contraction of both ventricular myocytes and mouse heart. In particular, antibodies binding to the RSATEEEPPNDD (SEQ ID NO: 1) or DVEDSYGQQWTYEQR (SEQ ID NO: 2) peptides (or isoforms/derivatives thereof) of the alpha-subunit of the (Na++K+)-ATPase, have been found to be highly inotropic. Both the antibodies and the peptides are important for the treatment of human heart failure and other contractile disorders.

Abstract: Antibodies binding to sites on the ?-subunit (Na++K+)-ATPase increase cardiac contraction of both ventricular myocytes and mouse heart. In particular, antibodies binding to the RSATEEEPPNDD (SEQ ID NO: 1) or DVEDSYGQQWTYEQR (SEQ ID NO: 2) peptides (or isoforms/derivatives thereof) of the ?-subunit of the (Na++K+)-ATPase, have been found to be highly inotropic. Both the antibodies and the peptides are important for the treatment of human heart failure and other contractile disorders.

Abstract: Antibodies binding to sites on the &agr;-subunit (Na++K+)-ATPase increase cardiac contraction of both ventricular myocytes and mouse heart. In particular, antibodies binding to the RSATEEEPPNDD or DVEDSYGQQWTYEQR peptides (or isoforms/derivatives thereof) of the &agr;-subunit of the (Na++K+)-ATPase, have been found to be highly inotropic. Both the antibodies and the peptides are important for the treatment of human heart failure and other contractile disorders.

Abstract: 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.