Autoantibodies against the beta 1-adrenoceptor from patients with dilated cardiomyopathy prolong action potential duration and enhance contractility in isolated cardiomyocytes

Item Type:	Article
Title:	Autoantibodies against the beta 1-adrenoceptor from patients with dilated cardiomyopathy prolong action potential duration and enhance contractility in isolated cardiomyocytes
Creators Name:	Christ, T. and Wettwer, E. and Dobrev, D. and Adolph, E. and Knaut, M. and Wallukat, G. and Ravens, U.
Abstract:	Autoantibodies against the β1-adrenoceptor ({beta}1-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 {beta}1-AAB affect electrophysiological properties and cell shortening of isolated cardiomyocytes 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 atria. The unselective {beta}-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 {beta}1-AAB, whereas flow through of the chromatography column was ineffective. (-)-Isoprenaline prolonged APD to the same extent during plateau and late phase of repolarization. {beta}1-AAB increased L-Type Ca2+ current in correspondence with the prolongation of APD. The effects of {beta}1-AAB and (-)-isoprenaline on APD were strongly attenuated after preincubation of the myocytes with the selective {beta}1-adrenoceptor antagonist (-)-bisoprolol. In addition, {beta}1-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 via {beta}1-adrenoceptors. These effects may contribute to β1-adrenoceptor-mediated cardiotoxicity in heart failure.
Keywords:	{Beta}-Adrenoceptors, Action Potentials, Autoantibodies, Cardiomyopathy, Myocytes, Animals, Rats
Source:	Journal of Molecular and Cellular Cardiology
ISSN:	0022-2828
Publisher:	Elsevier
Volume:	33
Number:	8
Page Range:	1515-1525
Date:	1 January 2001
Official Publication:	https://doi.org/10.1006/jmcc.2001.1414
PubMed:	View item in PubMed

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