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Pro-arrhythmogenic effects of Trypanosoma cruzi conditioned medium proteins in a model of bovine chromaffin cells

Published online by Cambridge University Press:  13 August 2021

A. M. Baraibar Open the ORCID record for A. M. Baraibar [Opens in a new window] ,
R. de Pascual ,
H. O. Rodriguez Angulo ,
A. Mijares  and
J. M. Hernández-Guijo
A. M. Baraibar
Affiliation:
Department of Neuroscience, University of Minnesota, 4-158 Jackson Hall, 321 Church St s.e., Minneapolis, MN55455, USA
R. de Pascual
Affiliation:
Department of Pharmacology and Therapeutic, Universidad Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029Madrid, Spain Institute ‘Teófilo Hernando’, Universidad Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029Madrid, Spain
H. O. Rodriguez Angulo
Affiliation:
Laboratorio de Fisiología de Parásitos, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
A. Mijares
Affiliation:
Laboratorio de Fisiología de Parásitos, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
J. M. Hernández-Guijo*
Affiliation:
Department of Pharmacology and Therapeutic, Universidad Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029Madrid, Spain Institute ‘Teófilo Hernando’, Universidad Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029Madrid, Spain IRYCIS, School of Medicine, Universidad Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029Madrid, Spain
*
Author for correspondence: J. M. Hernández-Guijo, E-mail: jesusmiguel.hernandez@uam.es
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Abstract

Asymptomatic sudden death is the principal cause of mortality in Chagas disease. There is little information about molecular mechanisms involved in the pathophysiology of malignant arrhythmias in Chagasic patients. Previous studies have involved Trypanosoma cruzi secretion proteins in the genesis of arrhythmias ex vivo, but the molecular mechanisms involved are still unresolved. Thus, the aim was to determine the effect of these secreted proteins on the cellular excitability throughout to test its effects on catecholamine secretion, sodium-, calcium-, and potassium-conductance and action potential (AP) firing. Conditioned medium was obtained from the co-culture of T. cruzi and Vero cells (African green monkey kidney cells) and ultra-filtered for concentrating immunogenic high molecular weight parasite proteins. Chromaffin cells were assessed with the parasite and Vero cells control medium. Parasite-secreted proteins induce catecholamine secretion in a dose-dependent manner. Additionally, T. cruzi conditioned medium induced depression of both calcium conductance and calcium and voltage-dependent potassium current. Interestingly, this fact was related to the abolishment of the hyperpolarization phase of the AP produced by the parasite medium. Taken together, these results suggest that T. cruzi proteins may be involved in the genesis of pro-arrhythmic conditions that could influence the appearance of malignant arrhythmias in Chagasic patients.

Keywords

Action potentialscalcium channelscatecholamine secretionChromaffin cellsT. cruzi
Type
Research Article
Information
Parasitology , Volume 148 , Issue 13 , November 2021 , pp. 1612 - 1623
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

A. M. Baraibar and R. de Pascual have contributed equally to this work.

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