Autoantibodies Against the β1adrenoceptor from Patients with Dilated Cardiomyopathy Prolong Action Potential Duration and Enhance Contractility in Isolated Cardiomyocytes

Autoantibodies against the β1-adrenoceptor (β1-AAB) from patients with dilated cardiomyopathy (DCM) increase the beating frequency of cultured neonatal rat cardiomyocytes. This effect is accompanied by only a small increase in cAMP production. Here we have investigated whether β1-AAB affect electrophysiological properties and cell shortening of isolated cardiomyocytes by interacting with theβ1 -adrenoceptor. β1-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 atria. The unselective β -adrenoceptor agonist (−)-isoprenaline was studied for comparison. Immunoglobulin G(IgG) antibodies increased the spontaneous 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 late than on early repolarization phases. Similar effects were obtained with purified β1-AAB, whereas flow through of the chromatography column was ineffective. (−)-Isoprenaline prolonged APD to the same extent during plateau and late phase of repolarization. β1-AAB increased L-Type Ca2+current in correspondence with the prolongation of APD. The effects of β1-AAB and (−)-isoprenaline on APD were strongly attenuated after preincubation of the myocytes with the selective β1-adrenoceptor antagonist (−)-bisoprolol. In addition, β1-AAB increased cell shortening in ventricular myocytes from adult rat hearts.β1 -AAB enhancing the beating frequency of cultured cardiomyocytes, increase L-Type Ca2+current, APD and contractility in freshly isolated cardiomyocytes mediated viaβ1 -adrenoceptors. These effects may contribute to β1-adrenoceptor-mediated cardiotoxicity in heart failure.