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Pro-arrhythmogenic Effects of Conditioned Medium Proteins in a Model of Bovine Chromaffin Cells

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Journal Parasitology
Specialty Parasitology
Date 2021 Aug 13
PMID 34384512
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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.

References
1.
Escobar A, Fernandez-Gomez R, Peter J, Mobini R, Hoebeke J, Mijares A . IgGs and Mabs against the beta2-adrenoreceptor block A-V conduction in mouse hearts: A possible role in the pathogenesis of ventricular arrhythmias. J Mol Cell Cardiol. 2006; 40(6):829-37. DOI: 10.1016/j.yjmcc.2006.03.430. View

2.
Rodriguez-Angulo H, Toro-Mendoza J, Marques J, Concepcion J, Bonfante-Cabarcas R, Higuerey Y . Evidence of reversible bradycardia and arrhythmias caused by immunogenic proteins secreted by T. cruzi in isolated rat hearts. PLoS Negl Trop Dis. 2015; 9(2):e0003512. PMC: 4315581. DOI: 10.1371/journal.pntd.0003512. View

3.
Hernandez C, Barcellos L, Gimenez L, Cabarcas R, Garcia S, Pedrosa R . Human chagasic IgGs bind to cardiac muscarinic receptors and impair L-type Ca2+ currents. Cardiovasc Res. 2003; 58(1):55-65. DOI: 10.1016/s0008-6363(02)00811-8. View

4.
Albinana E, Segura-Chama P, Baraibar A, Hernandez-Cruz A, Hernandez-Guijo J . Different contributions of calcium channel subtypes to electrical excitability of chromaffin cells in rat adrenal slices. J Neurochem. 2015; 133(4):511-21. DOI: 10.1111/jnc.13055. View

5.
Mijares A, Espinosa R, Adams J, Lopez J . Increases in [IP3]i aggravates diastolic [Ca2+] and contractile dysfunction in Chagas' human cardiomyocytes. PLoS Negl Trop Dis. 2020; 14(4):e0008162. PMC: 7176279. DOI: 10.1371/journal.pntd.0008162. View