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Title

Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes

Authors
Paci, Michelangelo
Sartiani, Laura
Del Lungo, Martina
Jaconi, Marisa
Mugelli, Alessandro
Cerbai, Elisabetta
Severi, Stefano
Published in Biomedical Engineering Online. 2012, vol. 11, 61
Abstract BACKGROUND: Human embryonic stem cell derived cardiomyocytes (hESC-CMs) hold high potential for basic and applied cardiovascular research. The development of a reliable simulation platform able to mimic the functional properties of hESC-CMs would be of considerable value to perform preliminary test complementing in vitro experimentations. METHODS: We developed the first computational model of hESC-CM action potential by integrating our original electrophysiological recordings of transient-outward, funny, and sodium-calcium exchanger currents and data derived from literature on sodium, calcium and potassium currents in hESC-CMs. RESULTS: The model is able to reproduce basal electrophysiological properties of hESC-CMs at 15 40 days of differentiation (Early stage). Moreover, the model reproduces the modifications occurring through the transition from Early to Late developmental stage (50-110, days of differentiation). After simulated blockade of ionic channels and pumps of the sarcoplasmic reticulum, Ca2+ transient amplitude was decreased by 12% and 33% in Early and Late stage, respectively, suggesting a growing contribution of a functional reticulum during maturation. Finally, as a proof of concept, we tested the effects induced by prototypical channel blockers, namely E4031 and nickel, and their qualitative reproduction by the model. CONCLUSIONS: This study provides a novel modelling tool that may serve useful to investigate physiological properties of hESC-CMs.
Identifiers
PMID: 22929020
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Article (Published version) (451 Kb) - public document Free access
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Research group Mécanismes de différentiation cellulaire des cellules cardiaques (536)
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PACI, Michelangelo et al. Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes. In: Biomedical Engineering Online, 2012, vol. 11, p. 61. doi: 10.1186/1475-925X-11-61 https://archive-ouverte.unige.ch/unige:26276

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Deposited on : 2013-02-07

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