TUTCRIS - Tampereen teknillinen yliopisto

TUTCRIS

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

Tutkimustuotosvertaisarvioitu

Yksityiskohdat

AlkuperäiskieliEnglanti
Artikkeli61
JulkaisuBioMedical Engineering Online
Vuosikerta11
DOI - pysyväislinkit
TilaJulkaistu - 28 elokuuta 2012
OKM-julkaisutyyppiA1 Alkuperäisartikkeli

Tiivistelmä

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.