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

Cells

Beatriz Trenor¹  Javier Saiz¹  Jorge Sánchez²  Olaf Dössel²  Axel Loewe² 

[1] Centro de Investigación e Innovación en Bioingeniería (Ci2B), Universitàt Politècnica de València, 46022 Valencia, Spain;Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany;

关键词: myofibroblast;    fibrosis;    atrial fibrillation;    calcium handling;   

DOI  :  10.3390/cells10112852

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown