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

Sánchez, Jorge 1; Trenor, Beatriz; Saiz, Javier; Dössel, Olaf 1; Loewe, Axel ORCID iD icon 1
1 Institut für Biomedizinische Technik (IBT), Karlsruher Institut für Technologie (KIT)

Abstract (englisch):

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 Ca$^{2+}$ 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 Ca$^{2+}$ currents can explain the experimentally observed variability regarding the myofibroblast resting membrane potential. The presence of an L-type Ca$^{2+}$ 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 Ca$^{2+}$ 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. ... mehr

Verlagsausgabe §
DOI: 10.5445/IR/1000141821
Veröffentlicht am 12.01.2022
DOI: 10.3390/cells10112852
Zitationen: 6
Web of Science
Zitationen: 6
Zitationen: 8
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biomedizinische Technik (IBT)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2021
Sprache Englisch
Identifikator ISSN: 2073-4409
KITopen-ID: 1000141821
Erschienen in Cells
Verlag MDPI
Band 10
Heft 11
Seiten Art.Nr.: 2852
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Vorab online veröffentlicht am 22.10.2021
Schlagwörter myofibroblast; fibrosis; atrial fibrillation; calcium handling
Nachgewiesen in Web of Science
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