{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T05:38:55Z","timestamp":1775281135501,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009137","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000}}],"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-IAHU-04"],"award-info":[{"award-number":["ANR-10-IAHU-04"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["16 CVD 02"],"award-info":[{"award-number":["16 CVD 02"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The pig is commonly used as an experimental model of human heart disease, including for the study of mechanisms of arrhythmia. However, there exist differences between human and porcine cellular electrophysiology: The pig action potential (AP) has a deeper phase-1 notch, a longer duration at 50% repolarization, and higher plateau potentials than human. Ionic differences underlying the AP include larger rapid delayed-rectifier and smaller inward-rectifier K<jats:sup>+<\/jats:sup>-currents (I<jats:sub>Kr<\/jats:sub> and I<jats:sub>K1<\/jats:sub> respectively) in humans. AP steady-state rate-dependence and restitution is steeper in pigs. Porcine Ca<jats:sup>2+<\/jats:sup> transients can have two components, unlike human. Although a reliable computational model for human ventricular myocytes exists, one for pigs is lacking. This hampers translation from results obtained in pigs to human myocardium. Here, we developed a computational model of the pig ventricular cardiomyocyte AP using experimental datasets of the relevant ionic currents, Ca<jats:sup>2+<\/jats:sup>-handling, AP shape, AP duration restitution, and inducibility of triggered activity and alternans. To properly capture porcine Ca<jats:sup>2+<\/jats:sup> transients, we introduced a two-step process with a faster release in the t-tubular region, followed by a slower diffusion-induced release from a non t-tubular subcellular region. The pig model behavior was compared with that of a human ventricular cardiomyocyte (O\u2019Hara-Rudy) model. The pig, but not the human model, developed early afterdepolarizations (EADs) under block of I<jats:sub>K1<\/jats:sub>, while I<jats:sub>Kr<\/jats:sub> block led to EADs in the human but not in the pig model. At fast rates (pacing cycle length = 400 ms), the human cell model was more susceptible to spontaneous Ca<jats:sup>2+<\/jats:sup> release-mediated delayed afterdepolarizations (DADs) and triggered activity than pig. Fast pacing led to alternans in human but not pig. Developing species-specific models incorporating electrophysiology and Ca<jats:sup>2+-<\/jats:sup>handling provides a tool to aid translating antiarrhythmic and arrhythmogenic assessment from the bench to the clinic.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009137","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T17:49:49Z","timestamp":1625075389000},"page":"e1009137","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["A computational model of pig ventricular cardiomyocyte electrophysiology and calcium handling: Translation from pig to human electrophysiology"],"prefix":"10.1371","volume":"17","author":[{"given":"Namit","family":"Gaur","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Yan","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-3451","authenticated-orcid":true,"given":"David","family":"Benoist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-5791","authenticated-orcid":true,"given":"Olivier","family":"Bernus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"Coronel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley","family":"Nattel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-3589","authenticated-orcid":true,"given":"Edward J.","family":"Vigmond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"pcbi.1009137.ref001","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1093\/europace\/eux104","article-title":"Progressive increase of the T peak-T end interval is associated with ischaemia-induced ventricular fibrillation in a porcine myocardial infarction model","volume":"20","author":"JE Azarov","year":"2017","journal-title":"EP Europace"},{"issue":"12","key":"pcbi.1009137.ref002","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1016\/j.cjca.2019.07.622","article-title":"Animal models of repaired tetralogy of fallot: current applications and future perspectives","volume":"35","author":"E Valdeomillos","year":"2019","journal-title":"Canadian Journal of Cardiology"},{"key":"pcbi.1009137.ref003","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/j.hrthm.2017.06.025","article-title":"Shivkumar, Ardell JL. Bioelectronic block of paravertebral sympathetic nerves mitigates post\u2014myocardial infarction ventricular arrhythmias","volume":"14","author":"RW Chui","year":"2017","journal-title":"Heart Rhythm"},{"key":"pcbi.1009137.ref004","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.hrthm.2017.04.001","article-title":"Role of suppression of the inward rectifier current in terminal action potential repolarization in the failing heart","volume":"14","author":"MG Klein","year":"2017","journal-title":"Heart Rhythm"},{"key":"pcbi.1009137.ref005","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ijcard.2018.05.113","article-title":"Cardioprotective effect of substance P in a porcine model of acute myocardial infarction","volume":"271","author":"DS Sim","year":"2018","journal-title":"International Journal of Cardiology"},{"key":"pcbi.1009137.ref006","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1172\/JCI76919","article-title":"Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias","volume":"125","author":"DS Park","year":"2015","journal-title":"Journal of Clinical Investigation"},{"key":"pcbi.1009137.ref007","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.yjmcc.2006.08.001","article-title":"Dietary fish oil reduces the occurrence of early afterdepolarizations in pig ventricular myocytes","volume":"41","author":"HM Den Ruijter","year":"2006","journal-title":"Journal of Molecular and Cellular Cardiology"},{"key":"pcbi.1009137.ref008","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.cardiores.2006.02.022","article-title":"Incorporated sarcolemmal fish oil fatty acids shorten pig ventricular action potentials","volume":"70","author":"AO Verkerk","year":"2006","journal-title":"Cardiovascular Research"},{"key":"pcbi.1009137.ref009","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1016\/j.hrthm.2007.07.015","article-title":"Dietary fish oil reduces the 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Roden","year":"1998","journal-title":"Taking the \u201cidio\u201d out of \u201cidiosyncratic\u201d: predicting torsades de pointes, Pacing and Clinical Electrophysiology"},{"key":"pcbi.1009137.ref031","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1161\/01.CIR.72.5.1092","article-title":"Cesium chloride-induced long QT syndrome: demonstration of afterdepolarizations and triggered activity in vivo","volume":"7","author":"JH Levine","year":"1985","journal-title":"Circulation"},{"key":"pcbi.1009137.ref032","doi-asserted-by":"crossref","first-page":"H2597","DOI":"10.1152\/ajpheart.00393.2006","article-title":",Electrophysiological mechanisms of ventricular arrhythmias in relation to Andersen-Tawil syndrome under conditions of reduced I K1: a simulation study","volume":"291","author":"RJ Sung","year":"2006","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"key":"pcbi.1009137.ref033","doi-asserted-by":"crossref","first-page":"H1023","DOI":"10.1152\/ajpheart.00785.2011","article-title":"Quantitative comparison of cardiac ventricular myocyte electrophysiology and response to drugs in human and nonhuman species. 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