{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:13:03Z","timestamp":1783573983183,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health and Research","doi-asserted-by":"publisher","award":["81150"],"award-info":[{"award-number":["81150"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health and Research","doi-asserted-by":"publisher","award":["162181"],"award-info":[{"award-number":["162181"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["HL-66140"],"award-info":[{"award-number":["HL-66140"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>During acute coronary occlusion, ischemia is a major determinant of the cell response to subsequent reperfusion and is the major precursor of the typical \u201cischemia\u2013reperfusion injury\u201d (IRI). Therefore, elucidating the full IRI process primarily relies on a good understanding of ischemia-induced alterations. Ischemic arrhythmias frequently arise during the acute phase of a myocardial infarction (MI) and originate in the terminal arborisations of the cardiac conduction system. These ventricular arrhythmias are triggered by abnormal Ca2+-dependent depolarisations (DADs) of Purkinje cells (Pcells) due to increased spontaneous Ca2+ release by the sarcoplasmic reticulum (SR). This early alteration of the conduction tissue is also likely to provide a substrate for IRI-related arrhythmogenicity. Recent evidence associates the ischemic phase of the MI with a significant increase in SERCA2 pump expression in Pcells, suggesting that enhanced SR-Ca2+ release results from an augmentation of Ca2+ sequestration by the SR in those cells. We examined this hypothesis by assessing the impact of ischemia on the dynamics of SR-Ca2+ uptake in live Pcells by high-resolution confocal microscopy in a classical canine model of LAD coronary ligation. Pcells from five normal hearts were compared with cells from five hearts 48 Hrs after coronary occlusion. Purkinje-specific Ca2+ events, namely peripheral Ca2+ wavelets (Wlets) and central cell-wide waves (CWWs), were analysed to assess the regional SR-Ca2+ transport of Pcells. A total of 83 normal and 126 MI Wlets, along with 10 normal and 30 MI CWWs, were analysed to compare the peripheral and central SR-Ca2+ transports of Pcells between normal and ischemic hearts. Forty-eight hours following the onset of ischemia, individual SR-Ca2+ release sites exhibited a 60% increase in Ca2+ spark firing rate. However, the site density remained unchanged, indicating an acceleration of intra-SR-Ca2+ cycling rather than direct alteration of the SR-Ca2+ release channels. While central CWWs remained unchanged, a 37% acceleration of resting Ca2+ restoration was readily visible in peripheral Wlets, consistent with enhanced SR-Ca2+ uptake at the cell periphery. Computational modelling reproduced these findings when the Ca2+ uptake rate was numerically increased by 35%, confirming that augmented SERCA activity is sufficient to explain the pro-arrhythmic SR-Ca2+ release of Pcells after MI. Our findings confirm that the augmentation of Ca2+ pump density in the periphery of Pcells is associated with an increase in SR-Ca2+ uptake, explaining the arrhythmogenicity of Purkinje fibres in an ischemic heart. This ischemia-mediated pro-arrhythmic remodelling of intracellular Ca2+ handling in the conduction system is also likely to contribute to triggered activity during subsequent reperfusion.<\/jats:p>","DOI":"10.3390\/cells15131196","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:50:37Z","timestamp":1782867037000},"page":"1196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased Ca2+ Sequestration by the Sarco-\/Endoplasmic Reticulum in Cardiac Purkinje Cells After Myocardial Infarction"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3566-4205","authenticated-orcid":false,"given":"Ruhul","family":"Amin","sequence":"first","affiliation":[{"name":"Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9779-468X","authenticated-orcid":false,"given":"Zhann\u00e9","family":"Hopkinson","sequence":"additional","affiliation":[{"name":"Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2159-9693","authenticated-orcid":false,"given":"Louisa","family":"Wiede","sequence":"additional","affiliation":[{"name":"Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazi T.","family":"Haq","sequence":"additional","affiliation":[{"name":"Children\u2019s National Hospital, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope A.","family":"Boyden","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Centre for Molecular Therapeutics, Columbia University, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk E. D. J.","family":"ter Keurs","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7744-3748","authenticated-orcid":false,"given":"Bruno D.","family":"Stuyvers","sequence":"additional","affiliation":[{"name":"Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1161\/01.CIR.0000027564.55739.B1","article-title":"Mapping and ablation of idiopathic ventricular fibrillation","volume":"106","author":"Shoda","year":"2002","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.jacc.2004.08.034","article-title":"Mapping and ablation of polymorphic ventricular tachycardia after myocardial infarction","volume":"44","author":"Szumowski","year":"2004","journal-title":"J. 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