{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T21:45:07Z","timestamp":1787694307793,"version":"build-2784847793"},"reference-count":93,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["LO2093\/1-1"],"award-info":[{"award-number":["LO2093\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DO637\/22-3"],"award-info":[{"award-number":["DO637\/22-3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European High-Performance Computing","award":["No 955495 (MICROCARD)"],"award-info":[{"award-number":["No 955495 (MICROCARD)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>During atrial fibrillation, cardiac tissue undergoes different remodeling processes at different scales from the molecular level to the tissue level. One central player that contributes to both electrical and structural remodeling is the myofibroblast. Based on recent experimental evidence on myofibroblasts\u2019 ability to contract, we extended a biophysical myofibroblast model with Ca2+ handling components and studied the effect on cellular and tissue electrophysiology. Using genetic algorithms, we fitted the myofibroblast model parameters to the existing in vitro data. In silico experiments showed that Ca2+ currents can explain the experimentally observed variability regarding the myofibroblast resting membrane potential. The presence of an L-type Ca2+ current can trigger automaticity in the myofibroblast with a cycle length of 799.9 ms. Myocyte action potentials were prolonged when coupled to myofibroblasts with Ca2+ handling machinery. Different spatial myofibroblast distribution patterns increased the vulnerable window to induce arrhythmia from 12 ms in non-fibrotic tissue to 22 \u00b1 2.5 ms and altered the reentry dynamics. Our findings suggest that Ca2+ handling can considerably affect myofibroblast electrophysiology and alter the electrical propagation in atrial tissue composed of myocytes coupled with myofibroblasts. These findings can inform experimental validation experiments to further elucidate the role of myofibroblast Ca2+ handling in atrial arrhythmogenesis.<\/jats:p>","DOI":"10.3390\/cells10112852","type":"journal-article","created":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T22:06:16Z","timestamp":1635113176000},"page":"2852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-2691","authenticated-orcid":false,"given":"Jorge","family":"S\u00e1nchez","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Trenor","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n e Innovaci\u00f3n en Bioingenier\u00eda (Ci2B), Universit\u00e0t Polit\u00e8cnica de Val\u00e8ncia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9850-0825","authenticated-orcid":false,"given":"Javier","family":"Saiz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n e Innovaci\u00f3n en Bioingenier\u00eda (Ci2B), Universit\u00e0t Polit\u00e8cnica de Val\u00e8ncia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4551-7970","authenticated-orcid":false,"given":"Olaf","family":"D\u00f6ssel","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-4744","authenticated-orcid":false,"given":"Axel","family":"Loewe","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.cardiores.2004.08.020","article-title":"Structural and functional characterisation of cardiac fibroblasts","volume":"65","author":"Camelliti","year":"2005","journal-title":"Cardiovasc. 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