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

Research output: Contribution to journalArticleScientificpeer-review

Details

Original languageEnglish
Article number61
JournalBioMedical Engineering Online
Volume11
DOIs
Publication statusPublished - 28 Aug 2012
Publication typeA1 Journal article-refereed

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, Ca 2+ 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.

Keywords

  • Action potential, Computer simulation, Embryonic stem cells, Pharmacology