A novel ionic model for matured and paced atrial-like human iPSC-CMs integrating IKur and IKCa currents
Informazioni aggiuntive
Autori
Tipo
Articolo pubblicato in rivista scientifica
Anno
2024
Lingua
Inglese
Sommario
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.
Parole chiave
hiPSC-CMs , Atrial phenotype , Ionic model , Dynamic clamp , Atrial-specific currents , Optimization tools
Periodico
Computers in Biology and Medicine
Volume
180
Pagine (o numero dell’articolo)
108899
Diffusione
Licenza
CC BY
Visibilità
Pubblico
Status open access
Hybrid
