A novel ionic model for matured and paced atrial-like human iPSC-CMs integrating IKur and IKCa currents
- Botti, Sofia ORCID Euler Institute (EUL), Università della Svizzera italiana, Switzerland - Department of Mathematics ‘‘Felice Casorati", University of Pavia, Italy
- Bartolucci, Chiara Department of Electrical, Electronic, and Information Engineering ‘‘Guglielmo Marconi’’, University of Bologna, Cesena, Italy
- Altomare, Claudia Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale, Lugano, Switzerland - Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland - Euler Institute (EUL), Università della Svizzera italiana, Switzerland
- Paci, Michelangelo Department of Electrical, Electronic, and Information Engineering ‘‘Guglielmo Marconi’’, University of Bologna, Cesena, Italy
- Barile, Lucio ORCID Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale, Lugano, Switzerland - Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland - Euler Institute (EUL), Università della Svizzera italiana, Switzerland
- Krause, Rolf ORCID Euler Institute (EUL), Università della Svizzera italiana, Switzerland - Faculty of Mathematics and Informatics, UniDistance, Brig, Switzerland
- Pavarino, Luca Franco Department of Mathematics ‘‘Felice Casorati", University of Pavia, Italy
- Severi, Stefano Department of Electrical, Electronic, and Information Engineering ‘‘Guglielmo Marconi’’, University of Bologna, Cesena, Italy
- 2024
Published in:
- Computers in Biology and Medicine. - 2024, vol. 180, p. 108899
English
This work introduces the first atrial-specific in-silico human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) model, based on a set of phenotype-specific
and membrane currents. This model is built on novel in-vitro experimental data recently published by some of the co-authors to simulate the paced action potential of matured atrial-like hiPSC-CMs. The model consists of a system of stiff ordinary differential equations depending on several parameters, which have been tuned by automatic optimization techniques to closely match selected experimental biomarkers. The new model effectively simulates the electronic in-vitro hiPSC-CMs maturation process, transitioning from an unstable depolarized membrane diastolic potential to a stable hyperpolarized resting potential, and exhibits spontaneous firing activity in unpaced conditions. Moreover, our model accurately reflects the experimental rate dependence data at different cycle length and demonstrates the expected response to a specific current blocker. This atrial-specific in-silico model provides a novel computational tool for electrophysiological studies of cardiac stem cells and their applications to drug evaluation and atrial fibrillation treatment.
and membrane currents. This model is built on novel in-vitro experimental data recently published by some of the co-authors to simulate the paced action potential of matured atrial-like hiPSC-CMs. The model consists of a system of stiff ordinary differential equations depending on several parameters, which have been tuned by automatic optimization techniques to closely match selected experimental biomarkers. The new model effectively simulates the electronic in-vitro hiPSC-CMs maturation process, transitioning from an unstable depolarized membrane diastolic potential to a stable hyperpolarized resting potential, and exhibits spontaneous firing activity in unpaced conditions. Moreover, our model accurately reflects the experimental rate dependence data at different cycle length and demonstrates the expected response to a specific current blocker. This atrial-specific in-silico model provides a novel computational tool for electrophysiological studies of cardiac stem cells and their applications to drug evaluation and atrial fibrillation treatment.
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- English
- Classification
- Medicine
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CC BY
- Open access status
- hybrid
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- DOI 10.1016/j.compbiomed.2024.108899
- ARK ark:/12658/srd1331175
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- https://localhost:5000/ark:/12658/srd1331175
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