期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 33, 期 8, 页码 1515-1525出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1006/jmcc.2001.1414
关键词
autoantibodies; beta-adrenoceptors; cardiomyopathy; myocytes; action potentials
Autoantibodies against the beta (1)-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. beta (1)-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 beta (1)-adrenoceptor-mediated cardiotoxicity in heart failure. (C) 2001 Academic Press.
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