Hostname: page-component-76fb5796d-r6qrq Total loading time: 0 Render date: 2024-04-26T15:00:43.370Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access Rights & Permissions [Opens in a new window]

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
Check for updates
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

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

References

Akiyama, T, Yamazaki, T, Kawada, T, Shimizu, S, Sugimachi, M and Shirai, M (2010) Role of Ca2+-activated K+ channels in catecholamine release from in vivo rat adrenal medulla. Neurochemistry International 56, 263–269.CrossRefGoogle ScholarPubMed
Albiñana, E, Segura-Chama, P, Baraibar, AM, Hernández-Cruz, A and Hernández-Guijo, JM (2015) Different contributions of calcium channel subtypes to electrical excitability of chromaffin cells in rat adrenal slices. Journal of Neurochemistry 133, 511–521.CrossRefGoogle ScholarPubMed
Barr, SC, Pannabecker, TL, Gilmour, RF Jr and Chandler, JS (2003) Upregulation of cardiac cell plasma membrane calcium pump in a canine model of Chagas disease. The Journal of Parasitology 89, 381–384.CrossRefGoogle Scholar
Barrias, ES, de Carvalho, TM and de Souza, W (2013) Trypanosoma cruzi: entry into mammalian host cells and parasitophorous vacuole formation. Frontiers in Immunology 4, 186.CrossRefGoogle ScholarPubMed
Brossas, JY, Gulin, JEN, Bisio, MMC, Chapelle, M, Marinach-Patrice, C, Bordessoules, M, Palazon Ruiz, G, Vion, J, Paris, L, Altcheh, J and Mazier, D (2017) Secretome analysis of Trypanosoma cruzi by proteomics studies. PLoS ONE 12, e0185504.CrossRefGoogle ScholarPubMed
Burgoyne, RD and Alvarez de Toledo, G (2000) Fusion proteins and fusion pores workshop: regulated exocytosis and the vesicle cycle. EMBO Report 1, 304–307.CrossRefGoogle ScholarPubMed
Caradonna, KL and Burleigh, BA (2011) Mechanisms of host cell invasion by Trypanosoma cruzi. Advances in Parasitology 76, 33–61.CrossRefGoogle ScholarPubMed
Carbone, E, Borges, R, Eiden, LE, García, AG and Hernández-Cruz, A (2019) Chromaffin cells of the adrenal medulla: physiology, pharmacology, and disease. Comprehensive Physiology 9, 1443–1502.CrossRefGoogle Scholar
Chuenkova, MV and Pereiraperrin, M (2011) Neurodegeneration and neuroregeneration in Chagas disease. Advances in Parasitology 76, 195–233.CrossRefGoogle ScholarPubMed
Contreras, VT, Araque, W and Delgado, VS (1994) Trypanosoma cruzi: metacyclogenesis in vitro – I. Changes in the properties of metacyclic trypomastigotes maintained in the laboratory by different methods. Memórias do Instituto Oswaldo Cruz 89, 253–259.CrossRefGoogle ScholarPubMed
Daliry, A, Pereira, IR, Pereira-Junior, PP, Ramos, IP, Vilar-Pereira, G, Silvares, RR, Lannes-Vieira, J and Campos de Carvalho, AC (2014) Levels of circulating anti-muscarinic and anti-adrenergic antibodies and their effect on cardiac arrhythmias and dysautonomia in murine models of Chagas disease. Parasitology 141, 1769–1778.CrossRefGoogle ScholarPubMed
De Pablos, LM, Gonzalez, GG, Solano Parada, J, Seco Hidalgo, V, Diaz Lozano, IM, Gomez Samblas, MM, Bustos, TC and Osuna, A (2011) Differential expression and characterization of a member of the mucin-associated surface protein family secreted by Trypanosoma cruzi. Infection 79, 3993–4001.Google ScholarPubMed
Elliott, EB, McCarroll, D, Hasumi, H, Welsh, CE, Panissidi, AA, Jones, NG, Rossor, CL, Tait, A, Smith, GL, Mottram, JC, Morrison, LJ and Loughrey, CM (2013) Trypanosoma brucei cathepsin-L increases arrhythmogenic sarcoplasmic reticulum-mediated calcium release in rat cardiomyocytes. Cardiovascular Research 100, 325–335.CrossRefGoogle ScholarPubMed
Escobar, AL, Fernandez-Gomez, R, Peter, JC, Mobini, R, Hoebeke, J and Mijares, A (2006) IgGs and Mabs against the beta2-adrenoreceptor block A-V conduction in mouse hearts: a possible role in the pathogenesis of ventricular arrhythmias. Journal of Molecular and Cellular Cardiology 40, 829–837.CrossRefGoogle Scholar
García, AG, García de Diego, AM, Gandía, L, Borges, R and García-Sancho, J (2006) Calcium signaling and exocytosis in adrenal chromaffin cells. Physiological Review 86, 1093–1131.CrossRefGoogle ScholarPubMed
Grassi, G and Ram, VS (2016) Evidence for a critical role of the sympathetic nervous system in hypertension. Journal of the American Society of Hypertension 10, 457–466.CrossRefGoogle ScholarPubMed
Hamill, OP, Marty, A, Neher, E, Sakmann, B and Sigworth, FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Archiv European Journal of Physiology 391, 85–100.CrossRefGoogle ScholarPubMed
Healy, C, Viles-Gonzalez, JF, Saenz, LC, Soto, M, Ramirez, JD and d'Avila, A (2015) Arrhythmias in chagasic cardiomyopathy. Cardiac Electrophysiology Clinics 7, 251–268.CrossRefGoogle ScholarPubMed
Hernandez-Guijo, JM, Gandía, L, de Pascual, R and Garcia, AG (1997) Differential effects of the neuroprotectant lubeluzole on bovine and mouse chromaffin cell calcium channel subtypes. British Journal of Pharmacology 122, 275–285.CrossRefGoogle ScholarPubMed
Hernandez, CC, Barcellos, LC, Gimenez, LE, Cabarcas, RA, Garcia, S, Pedrosa, RC, Matheus, JH, Kurtenbach, E, Masuda, MO and Campos de Carvalho, AC (2003) Human chagasic IgGs bind to cardiac muscarinic receptors and impair L-type Ca2+ currents. Cardiovascular Research 58, 55–65.CrossRefGoogle ScholarPubMed
Hlaing, T, DiMino, T, Kowey, PR and Yan, GX (2005) ECG repolarization waves: their genesis and clinical implications. Annals of Noninvasive Electrocardiology 10, 211–223.CrossRefGoogle ScholarPubMed
Jackson, Y, Varcher Herrera, M and Gascon, J (2014) Economic crisis and increased immigrant mobility: new challenges in managing Chagas disease in Europe. Bulletin of the World Health Organization 92, 771–772.CrossRefGoogle ScholarPubMed
Jones, EM, Colley, DG, Tostes, S, Lopes, ER, Vnencak-Jones, CL and McCurley, TL (1992) A Trypanosoma cruzi DNA sequence amplified from inflammatory lesions in human chagasic cardiomyopathy. Transactions of the Association of American Physicians 105, 182–189.Google ScholarPubMed
Katz, B and Miledi, R (1968) The role of calcium in neuromuscular facilitation. Journal of Physiology 195, 481–492.CrossRefGoogle ScholarPubMed
Kodirov, SA, Brunner, M, Nerbonne, JM, Buckett, P, Mitchell and, GF and Koren, G (2004) Attenuation of I(K,slow1) and I(K,slow2) in Kv1/Kv2DN mice prolongs APD and QT intervals but does not suppress spontaneous or inducible arrhythmias. American Journal of Physiology-Heart and Circulatory Physiology 286, H368–H374.CrossRefGoogle ScholarPubMed
Korn, SJ, Marty, A, Connor, JA and Horn, R (1991) Perforated patch recording. Journal of Neuroscience Methods 4, 264–273.Google Scholar
Lankipalli, RS, Zhu, T, Guo, D and Yan, GX (2005) Mechanisms underlying arrhythmogenesis in long QT syndrome. Journal of Electrocardiology 38, 69–73.CrossRefGoogle ScholarPubMed
Lingle, CJ, Martinez-Espinosa, PL, Guarina, L and Carbone, E (2018) Roles of Na+, Ca2+, and K+ channels in the generation of repetitive firing and rhythmic bursting in adrenal chromaffin cells. Pflügers Archiv European Journal of Physiology 470, 39–52.CrossRefGoogle Scholar
Livett, BG (1984) Adrenal medullary chromaffin cells in vitro. Physiological Reviews 64, 1103–1161.CrossRefGoogle ScholarPubMed
Lopez, JR, Espinosa, R, Landazuru, P, Linares, N, Allen, P and Mijares, A (2011) Dysfunction of diastolic [Ca(2)( + )] in cardiomyocytes isolated from chagasic patients. Revista Española de Cardiología 64, 456–462.Google ScholarPubMed
Lynn, MK, Bossak, BH and Sandifer, PA (2020) Contemporary autochthonous human Chagas disease in the USA. Acta Tropica 205, 105361.CrossRefGoogle ScholarPubMed
Marcantoni, A, Baldelli, P, Hernandez-Guijo, JM, Comunanza, V, Carabelli, V and Carbone, E (2007) L-type calcium channels in adrenal chromaffin cells: role in pace-making and secretion. Cell Calcium 42, 397–408.CrossRefGoogle ScholarPubMed
Marcantoni, A, Vandael, DH, Mahapatra, S, Carabelli, V, Sinnegger-Brauns, MJ, Striessnig, J and Carbone, E (2010) Loss of Cav1.3 channels reveals the critical role of L-type and BK channel coupling in pacemaking mouse adrenal chromaffin cells. Journal of Neurosciene 30, 491–504.CrossRefGoogle ScholarPubMed
Marques, J, Mendoza, I, Noya, B, Acquatella, H, Palacios, I and Marques-Mejias, M (2013) ECG manifestations of the biggest outbreak of Chagas disease due to oral infection in Latin-America. Archivos Brasileños de Cardiología 101, 249–254.Google ScholarPubMed
Marrion, NV and Tavalin, SJ (1998) Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons. Nature 395, 900–905.CrossRefGoogle ScholarPubMed
Marty, A and Neher, E (1985) Potassium channels in cultured bovine adrenal chromaffin cells. Journal of Physiology 367, 117–141.CrossRefGoogle ScholarPubMed
Mendoza, IMF, Marques, J, Misticchio, F, Matheus, A and Rodriguez, A (1999) Ventricular tachycardia in Chagas heart disease. Italian Cardiology 29, 247–250.Google Scholar
Mijares, A, Espinosa, R, Adams, J and Lopez, JR (2020) Increases in [IP3]i aggravates diastolic [Ca2+] and contractile dysfunction in Chagas’ human cardiomyocytes. PLoS Neglected Tropical Diseases 14, e0008162.CrossRefGoogle Scholar
Moro, MA, López, MG, Gandía, L, Michelena, P and García, AG (1990) Separation and culture of living adrenaline- and noradrenaline-containing cells from bovine adrenal medullae. Analytical Biochemistry 185, 243–248.CrossRefGoogle ScholarPubMed
Naraghi, M and Neher, E (1997) Linearized buffered Ca2+ diffusion in microdomains and its implications for calculation of [Ca2+] at the mouth of a calcium channel. Journal of Neuroscience 17, 6961–6973.CrossRefGoogle Scholar
Neher, E (1986) Concentration profiles of intracellular calcium in the presence of a diffusible chelator. In Heinemann, U, Klee, M, Neher, E and Singer, W (eds), Exp. Brain Res. Series 14: Calcium Electrogenesis and Neuronal Functioning. Vol. 14. Heidelberg: Springer, pp. 80–96.CrossRefGoogle Scholar
Prakriya, M and Lingle, CJ (1999) Activation of BK channels during brief depolarizations or action potential waveforms requires Ca2+ influx through L-and Q-type Ca2+ channels in rat chromaffin cells. Journal of Neurophysiology 81, 2267–2278.CrossRefGoogle ScholarPubMed
Prakriya, M and Lingle, CJ (2000) Activation of BK channels in rat chromaffin cells requires summation of Ca2+ influx from multiple Ca2+ channels. Journal of Neurophysiology 84, 1123–1135.CrossRefGoogle Scholar
Protti, DA and Uchitel, OD (1993) Transmitter release and presynaptic Ca2+ currents blocked by the spider toxinω-Aga-IVA. Neuroreport 5, 333–336.CrossRefGoogle Scholar
Rae, J, Cooper, K, Gates, P and Watsky, M (1991) Low access resistance perforated patch recordings using amphotericin B. Journal of Neuroscience Methods 37, 15–26.10.1016/0165-0270(91)90017-TCrossRefGoogle ScholarPubMed
Retana Moreira, L, Rodríguez Serrano, F and Osuna, A (2019) Extracellular vesicles of Trypanosoma cruzi tissue-culture cell-derived trypomastigotes: induction of physiological changes in non-parasitized culture cells. PLoS Neglected Tropical Diseases 13, e0007163. doi: 10.1371/journal.pntd.0007163CrossRefGoogle ScholarPubMed
Roberts, WM (1993) Spatial calcium buffering in saccular hair cells. Nature 363, 74–76.CrossRefGoogle ScholarPubMed
Rodriguez-Angulo, H, Toro-Mendoza, J, Marques, J, Bonfante-Cabarcas, R and Mijares, A (2013) Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium. Brazilian Journal of Medical and Biological Research 46, 58–64.CrossRefGoogle ScholarPubMed
Rodriguez-Angulo, HO, Toro-Mendoza, J, Marques, JA, Concepcion, JL, Bonfante-Cabarcas, R, Higuerey, Y, Thomas, LE, Balzano-Nogueira, L, López, JR and Mijares, A (2015) Evidence of reversible bradycardia and arrhythmias caused by immunogenic proteins secreted by T. cruzi in isolated rat hearts. PLoS Neglected Tropical Diseases 9, e0003512.CrossRefGoogle Scholar
Salazar, R, Castillo-Neyra, R, Tustin, AW, Borrini-Mayori, K, Naquira, C and Levy, MZ (2014) Bed bugs (Cimex lectularius) as vectors of Trypanosoma cruzi. American Journal of Tropical Medicine and Hygiene 92, 331–335.CrossRefGoogle ScholarPubMed
Scott, RS, Bustillo, D, Olivos-Oré, LA, Cuchillo-Ibañez, I, Barahona, MV, Carbone, E and Artalejo, AR (2011) Contribution of BK channels to action potential repolarisation at minimal cytosolic Ca2+ concentration in chromaffin cells. Pflügers Archiv European Journal of Physiology 462, 545–557.CrossRefGoogle ScholarPubMed
Shen, MJ and Zipes, DP (2014) Role of the autonomic nervous system in modulating cardiac arrhythmias. Circulation Research 114, 1004–1021.CrossRefGoogle ScholarPubMed
Sheng, M and Wyszynzki, M (1997) Ion channel targeting in neurons. Bioessays 19, 847–853.CrossRefGoogle ScholarPubMed
Solano, CR, Prakriya, M, Ding, JP and Lingle, CJ (1995) Inactivating and non-inactivating Ca2+ and voltage-dependent K+ current in rat adrenal chromaffin cells. Journal of Neuroscience 15, 6110–6123.Google Scholar
Stocker, M (2004) Ca2+-activated K+ channels: molecular determinants and function of the SK family. Nature Reviews 5, 768–770.CrossRefGoogle ScholarPubMed
Sun, L, Xiong, Y, Zeng, X, Wu, Y, Pan, N, Lingle, CJ, Qu, A and Ding, J (2009) Differential regulation of action potentials by inactivating and noninactivating BK channels in rat adrenal chromaffin cells. Biophysical Journal 97, 1832–1842.CrossRefGoogle ScholarPubMed
Takahashi, T and Momiyamaa, A (1993) Different types of calcium channels mediate central synaptic transmission. Nature 366, 156–158.CrossRefGoogle ScholarPubMed
Teixeira, VDP, Magalhaes, EDP, Castro, EC, Guimaraes, JV, Rodrigues, ML, Nascimento, RB and dos Reis, MA (1995) Cardiac weight in patients with chronic Chagas disease with Trypanosoma cruzi nests in the central vein of the adrenal glands. Arquivos Brasileiros de Cardiologia 64, 315–317.Google Scholar
Vandael, DH, Marcantoni, A, Mahapatra, S, Caro, A, Ruth, P, Zuccotti, A, Knipper, M and Carbone, E (2010) Ca(v)1.3 and BK channels for timing and regulating cell firing. Molecular Neurobiology 42, 185–198.CrossRefGoogle ScholarPubMed
Vandael, DH, Zuccotti, A, Striessnig, J and Carbone, E (2012) Ca(v)1.3-driven SK channel activation regulates pacemaking and spike frequency adaptation in mouse chromaffin cells. Journal of Neuroscience 32, 16345–16359.CrossRefGoogle ScholarPubMed
Villar, SR, Ronco, MT, Fernandez Bussy, R, Roggero, E, Lepletier, A, Manarin, R, Savino, W, Pérez, AR and Bottasso, O (2013) Tumor necrosis factor-alpha regulates glucocorticoid synthesis in the adrenal glands of Trypanosoma cruzi acutely-infected mice, the role of TNF-R1. PLoS ONE 8, e63814.CrossRefGoogle ScholarPubMed
Watanabe Costa, R, Batista, MF, Meneghelli, I, Vidal, RO, Nájera, CA, Mendes, AC, Andrade-Lima, IA, da Silveira, JF, Lopes, LR, Ferreira, LRP, Antoneli, F and Bahia, D (2020) Comparative analysis of the secretome and interactome of Trypanosoma cruzi and Trypanosoma rangeli reveals species specific immune response modulating proteins. Frontiers in Immunology 27 11, 1774.CrossRefGoogle ScholarPubMed
Wisgirda, ME and Dryer, SE (1994) Functional dependence of Ca2+ activated K+ current on L- and N-type Ca2+ channels: differences between chicken sympathetic and parasympathetic neurons suggest different regulatory mechanisms. Proceedings of the National Academy of Sciences of the USA 91, 2858–2862.CrossRefGoogle Scholar
Yoshida, N, Favoreto, S Jr, Ferreira, AT and Manque, PM (2000). Signal transduction induced in Trypanosoma cruzi metacyclic trypomastigotes during the invasion of mammalian cells. Brazilian Journal of Medical and Biological Research 33, 269–278.10.1590/S0100-879X2000000300003CrossRefGoogle ScholarPubMed