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Article

Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology

1
Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany
2
Centro de Investigación e Innovación en Bioingeniería (Ci2B), Universitàt Politècnica de València, 46022 Valencia, Spain
*
Author to whom correspondence should be addressed.
Academic Editors: Ursula Ravens and Rémi Peyronnet
Cells 2021, 10(11), 2852; https://doi.org/10.3390/cells10112852
Received: 13 August 2021 / Revised: 8 October 2021 / Accepted: 19 October 2021 / Published: 22 October 2021
(This article belongs to the Special Issue Electrical Remodeling in Cardiac Disease)
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’ 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 ± 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. View Full-Text
Keywords: myofibroblast; fibrosis; atrial fibrillation; calcium handling myofibroblast; fibrosis; atrial fibrillation; calcium handling
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MDPI and ACS Style

Sánchez, J.; Trenor, B.; Saiz, J.; Dössel, O.; Loewe, A. Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology. Cells 2021, 10, 2852. https://doi.org/10.3390/cells10112852

AMA Style

Sánchez J, Trenor B, Saiz J, Dössel O, Loewe A. Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology. Cells. 2021; 10(11):2852. https://doi.org/10.3390/cells10112852

Chicago/Turabian Style

Sánchez, Jorge, Beatriz Trenor, Javier Saiz, Olaf Dössel, and Axel Loewe. 2021. "Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology" Cells 10, no. 11: 2852. https://doi.org/10.3390/cells10112852

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