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Am J Physiol Heart Circ Physiol (July 15, 2004). doi:10.1152/ajpheart.00044.2004
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Submitted on January 21, 2004
Accepted on July 8, 2004

SERA FROM PATIENTS WITH IDIOPATHIC DILATED CARDIOMYOPATHY DECREASE L-TYPE CALCIUM CURRENTS IN CARDIOMYOCYTES ISOLATED FROM RABBITS

Cristiane del Corsso*, Antonio C Campos de Carvalho, Helena F Martino, and Wamberto A Varanda

* To whom correspondence should be addressed. E-mail: cdelcors{at}aecom.yu.edu.

Auto antibodies 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 aim was to detect the presence of those antibodies in the sera of patients with IDC and characterize their electrophysiological effects on cardiomyocytes from rabbits. Using ELISA immunoassays, we detected high titers of antibodies against muscarinic (M2) receptors in the sera of all IDC patients, while the detection of antibodies against the {beta}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 (about 26 %) in Isoproterenol (ISO) stimulated L-type Ca++ currents (ICa-ISO ) in rabbit ventricular myocytes, while the sera from healthy blood donors (HBD) 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 ICa-ISO did not cause any effect on K+ currents. We concluded that sera from IDC patients have auto antibodies 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.




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