{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:49:12Z","timestamp":1753890552352,"version":"3.41.2"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Chagas disease is produced by the parasite <jats:italic>Trypanosoma cruzi (T. cruzi)<\/jats:italic>, which is the leading cause of death and morbidity in Latin America. We have shown that in patients with Chagas cardiomyopathy, there is a chronic elevation of diastolic Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>d<\/jats:sub>), associated with deterioration to further address this issue, we explored the role Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchanger (NCX). Experiments were carried out in noninfected C57BL\/6 mice and infected with blood-derived trypomastigotes of the <jats:italic>T. cruzi<\/jats:italic> Y strain. Anesthetized mice were sacrificed and the cardiomyocytes were enzymatically dissociated. Diastolic [Ca<jats:sup>2+<\/jats:sup>] ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>d<\/jats:sub>) was measured using Ca<jats:sup>2+<\/jats:sup> selective microelectrodes in cardiomyocytes from control mice (CONT) and cardiomyocytes from <jats:italic>T. cruzi<\/jats:italic> infected mice in the early acute phase (EAP) at 20 dpi, in the acute phase (AP) at 40 dpi, and in the chronic phase (CP) at 120 dpi. [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>d<\/jats:sub> was 1.5-times higher in EAP, 2.6-times in AP, and 3.4-times in CP compared to CONT. Exploring the reverse mode activity of NCX, we replaced extracellular Na<jats:sup>+<\/jats:sup> in equivalent amounts with N-methyl-D-glucamine. Reduction of [Na<jats:sup>+<\/jats:sup>]<jats:sub>e<\/jats:sub> to 65 mM caused an increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>d<\/jats:sub> of 1.7 times in cardiomyocytes from CONT mice, 2 times in EAP infected mice, 2.4 times in AP infected mice and 2.8 in CP infected mice. The Na<jats:sup>+<\/jats:sup> free solution caused a further elevation of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>d<\/jats:sub> of 2.5 times in cardiomyocytes from CONT, 2.8 times in EAP infected mice, 3.1 times in AP infected mice, and 3.3 times in CP infected mice. Extracellular Ca<jats:sup>2+<\/jats:sup> withdrawal reduced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>d<\/jats:sub> in both CONT and cardiomyocytes from Chagas-infected mice and prevented the increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>d<\/jats:sub> induced by Na<jats:sup>+<\/jats:sup> depletion. Preincubation with 10\u00b5M KB-R7943 or in 1\u00b5M YM-244769 reduced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>d<\/jats:sub> in cardiomyocytes from infected mice, but not control mice. Furthermore, both NCX blockers prevented the increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>d<\/jats:sub> associated with exposure to a solution without Na<jats:sup>+<\/jats:sup>. These results suggest that Ca<jats:sup>2+<\/jats:sup> entry through the reverse NCX mode plays a significant role in the observed [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>d<\/jats:sub> dyshomeostasis in Chagas infected cardiomyocytes. Additionally, NCX inhibitors may be a viable therapeutic approach for treating patients with Chagas cardiomyopathy.<\/jats:p>","DOI":"10.3389\/fcimb.2022.890709","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T06:10:01Z","timestamp":1657174201000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of the Na+\/Ca2+ Exchanger in Aberrant Intracellular Ca2+ in Cardiomyocytes of Chagas-Infected Rodents"],"prefix":"10.3389","volume":"12","author":[{"given":"Jose R.","family":"Lopez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Linares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose A.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Mijares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cbpa.2014.05.005","article-title":"Inhibition of the Cardiac ATP-Dependent Potassium Current by KB-R7943","volume":"175","author":"Abramochkin","year":"2014","journal-title":"Comp. 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