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Cardiovascular Research 2003 58(1):55-65; doi:10.1016/S0008-6363(02)00811-8
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Human chagasic IgGs bind to cardiac muscarinic receptors and impair L-type Ca2+ currents

Ciria Carolina Quintero Hernándeza, Luciane Claudia Barcellosa, Luis Eduardo Díaz Giménezb, Rafael Armando Bonfante Cabarcasc, Simone Garciaa, Roberto Coury Pedrosad, Jose Hamilton Matheus Nascimentoa, Eleonora Kurtenbachb, Masako Oya Masudaa and Antonio Carlos Campos de Carvalhoa,*

aInstituto de Biofísica Carlos Chagas Filho, Universidade do Brasil, Rio de Janeiro, 21949-900 Rj, Brazil
bInstituto de Ciências Biomédicas, Universidade do Brasil, Rio de Janeiro, 21949-900 Rj, Brazil
cUniversidad Centroccidental ‘Lisandro Alvarado’, Barquisimeto, Venezuela
dHospital Universitário Clementino Fraga Filho, Universidade do Brasil, Rio de Janeiro, 21949-900 Rj, Brazil

* Corresponding author. Tel.: +55-21-2280-4399; fax: +55-21-2280-8193. acarlos{at}biof.ufrj.br

Objectives: Antibodies against cardiac G protein-coupled receptors have been reported in sera from chronic chagasic patients (CChP) and other non-parasitic cardiomyopathies, but the effects and underlying mechanism of interaction between these antibodies and heart cells are not fully established. To address this point, binding of antibodies purified from sera of CChP patients and normal blood donors (NBD) to cardiac muscarinic acetylcholine receptors (mAChR) and their effect on L-type Ca2+ currents were examined. Methods and Results: Saturation [3H]NMS binding experiments with porcine atrial membranes showed that Bmax in the presence of CChP-immunoglobulin G (IgG) decreased from 280.2±16.08 fmol/mg (control) to 91.00±5.98 fmol/mg, with no apparent change in KD, while NBD-IgG did not significantly alter these parameters. At the single channel level, CChP-IgG decreased both the fast and slow mean open times and Po (from 0.074±0.023 to 0.025±0.007) without changes in single channel conductance. I/V plots of isoproterenol-stimulated whole-cell L-type Ca2+ currents (ICa) from rabbit ventricular cardiomyocytes showed a significant reduction in peak ICa during perfusion with CChP-IgG (at 0 mV: from 10.61±2.97 to 8.45±2.54 pA/pF). NBD-IgGs had no effect on ICa. A CChP-IgG purified against a peptide corresponding to the second extracellular loop of the M2 receptor also impaired L-type Ca2+ currents. All effects of CChP-IgG were blocked by atropine. Conclusions: Our results show that antibodies from CChP bind to mAChR in a non-competitive manner and are able to activate the receptor in an agonist-like form resulting in L-type Ca2+ current inhibition.

KEYWORDS Ca-channel; Cardiomyopathy; Immunology; Receptors; Single channel currents


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