Autoantibodies against the beta(1)-adrenoceptor from patients with dilatedcardiomyopathy prolong action potential duration and enhance contractilityin isolated cardiomyocytes

Autoantibodies against the beta (1)-adrenoceptor (beta (1)-AAB) from patien ts with dilated cardiomyopathy (DCM) increase the beating frequency of cult ured neonatal rat cardiomyocytes. This effect is accompanied by only a smal l increase in cAMP production. Here we have investigated whether beta (1)-A AB affect electrophysiological properties and cell shortening of isolated c ardiomyocytes by interacting with the beta (1)-adrenoceptor. beta (1)-AAB were obtained during immunoadsorption of patients with DCM and were used for experiments in isolated myocytes cultured from neonatal rat hearts, or freshly isolated from adult rat ventricles or from human right a tria, The unselective beta -adrenoceptor agonist(-)-isoprenaline was studie d for comparison. Immunoglobulin G (IgG) antibodies increased the spontaneo us beating frequency of neonatal rat cardiomyocytes to a lesser degree than (-)-isoprenaline, but both effects were maximum and stable after 2 min. In rat ventricular and human atrial myocytes, IgG increased action potential duration (APD) in a concentration-dependent manner with larger effects on l ate than on early repolarization phases. Similar effects were obtained with purified beta (1)-AAB. whereas flow through of the chromatography column w as ineffective. (-)-Isoprenaline prolonged APD to the same extent during pl ateau and late phase of repolarization. beta (1)-AAB increased L-Type Ca2current in correspondence with the prolongation of APD. The effects of beta (1)-AAB and (-)-isoprenaline on APD were strongly attenuated after preincu bation of the myocytes with the selective beta (1)-adrenoceptor antagonist (-)-bisoprolol. In addition, beta (1)-AAB increased cell shortening in vent ricular myocytes from adult rat hearts. beta (1)-AAB enhancing the beating frequency of cultured cardiomyocytes, in crease L-Type Ca2+ current, APD and contractility in freshly isolated cardi omyocytes mediated via beta (1)-adrenoceptors. These effects may contribute to beta (1)-adrenoceptor-mediated cardiotoxicity in heart failure. (C) 200 1 Academic Press.