Sera from patients with idiopathic dilated cardiomyopathy decrease ICa in cardiomyocytes isolated from rabbits

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 287; no. 5; pp. H1928 - H1936
• Main Authors: del Corsso, Cristiane, de Carvalho, Antonio Carlos Campos, Martino, Helena Furtado, Varanda, Wamberto Antonio
• Format: Journal Article
• Language: English
• Published: United States 01.11.2004
• Subjects: Action Potentials; Adrenergic beta-Agonists - pharmacology; Adult; Aged; Animals; Autoantibodies - blood; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - metabolism; Cardiomyopathy, Dilated - blood; Enzyme-Linked Immunosorbent Assay; Female; Humans; Isoproterenol - pharmacology; Male; Middle Aged; Myocytes, Cardiac - metabolism; Patch-Clamp Techniques; Rabbits; Reaction Time; Receptor, Muscarinic M2 - immunology; Receptors, Adrenergic, beta-1 - immunology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00044.2004

1 Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14049-900; 2 Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21949-900; and 3 Laranjeiras National Institute of Cardiology, Rio de Janeiro, Rio de Janeiro 22240-002, Brazil Submitted 2 January 2004 ; accepted in final form 8 July 2004 Autoantibodies against muscarinic and adrenergic receptors have been found in the sera of patients with idiopathic dilated cardiomyopathy (IDC) and Chagas disease, but it is still unclear whether they can functionally interact with their respective receptors to modulate cardiac functions. In this study, our goal was to detect the presence of those antibodies in the sera of patients with IDC and characterize their electrophysiological effects on cardiomyocytes from rabbits. By using ELISA immunoassays, we detected high titers of antibodies against muscarinic M 2 receptors in the sera of all IDC patients, whereas the detection of antibodies against the 1 -receptor occurred in 50% of them. Electrophysiological experiments using the whole cell configuration of the patch-clamp technique showed that sera from 43% of IDC patients induced a significant decrease ( 26%) in isoproterenol-stimulated L-type Ca 2+ currents in rabbit ventricular myocytes, whereas the sera from healthy blood donors failed to do so. As expected, IDC sera also decreased the action potential duration (by 10.5%) due to a shortening of the plateau phase. Sera that reduced isoproterenol-stimulated L-type Ca 2+ currents did not cause any effect on K + currents. We conclude that sera from IDC patients have autoantibodies, which interact with muscarinic M 2 receptors of rabbit cardiomyocytes, acting in an agonist-like fashion. This action results in changes in electrogenesis, which, as often observed in patients with IDC, could initiate ventricular arrhythmias that lead to sudden death. calcium channel; electrophysiology; patch clamp; heart failure; autoimmune disease Address for reprint requests and other correspondence: C. del Corsso, Albert Einstein College of Medicine, Dept. of Neuroscience, 1410 Pelham Pkwy. S., Bronx, NY 10461 (E-mail: cdelcors{at}aecom.yu.edu )