Sera from patients with idiopathic dilated cardiomyopathy decrease ICa in cardiomyocytes isolated from rabbits.
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 M2 receptors in the sera of all IDC patients, whereas the detection of antibodies against the beta1-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 (approximately 26%) in isoproterenol-stimulated L-type Ca2+ 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 Ca2+ currents did not cause any effect on K+ currents. We conclude that sera from IDC patients have autoantibodies, which interact with muscarinic M2 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.
Del Corsso
Cristiane
C
Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14049-900, Brazil. cdelcors@aecom.yu.edu
de Carvalho
Antônio Carlos Campos
AC
Martino
Helena Furtado
HF
Varanda
Wamberto Antonio
WA
D000200:Action Potentials; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D011930:Reaction Time; D043585:Receptor, Muscarinic M2 / Q000276:immunology*; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*
D000318:Adrenergic beta-Agonists; D001323:Autoantibodies; D020746:Calcium Channels, L-Type; D043585:Receptor, Muscarinic M2; D018342:Receptors, Adrenergic, beta-1; D007545:Isoproterenol