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

Ciria Carolina Quintero Hernández1, Luciane Claudia Barcellos, Luis Eduardo Díaz Giménez

  • 1Instituto de Biofísica Carlos Chagas Filho, Universidade do Brasil, Rio de Janeiro, Brazil.

Cardiovascular Research
|April 2, 2003
PubMed

Insights

Antibodies from chronic chagasic patients (CChP) bind to cardiac muscarinic acetylcholine receptors (mAChR). This interaction inhibits L-type Ca(2+) currents, offering insights into Chagas disease cardiomyopathy mechanisms.

Area of Science:

  • Cardiology
  • Immunology
  • Molecular Biology

Background:

  • Cardiac G protein-coupled receptors are implicated in cardiomyopathies.
  • Antibodies against these receptors are found in chronic chagasic patients (CChP).
  • The precise mechanism of antibody interaction with cardiac cells remains unclear.

Purpose of the Study:

  • To investigate the binding of CChP-derived antibodies to cardiac muscarinic acetylcholine receptors (mAChR).
  • To determine the functional effects of these antibodies on L-type Ca(2+) currents in cardiomyocytes.

Main Methods:

  • Purified immunoglobulin G (IgG) from CChP and normal blood donors (NBD) were used.
  • Saturation binding assays with [3H]NMS on porcine atrial membranes.
  • Single-channel electrophysiology and whole-cell patch-clamp recordings of L-type Ca(2+) currents (I(Ca)) in rabbit ventricular cardiomyocytes.

Main Results:

  • CChP-IgG significantly reduced mAChR B(max) without altering K(D), indicating non-competitive binding.
  • CChP-IgG decreased single L-type Ca(2+) channel mean open times and open probability (P(o)).
  • CChP-IgG inhibited isoproterenol-stimulated whole-cell L-type Ca(2+) currents, an effect blocked by atropine.

Conclusions:

  • Antibodies from CChP bind to mAChR in a non-competitive manner.
  • These antibodies activate mAChR in an agonist-like fashion.
  • This activation leads to the inhibition of L-type Ca(2+) currents, contributing to cardiac dysfunction.
Abstract

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