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

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.

journal_name

Biomed Eng Online

authors

Paci M,Sartiani L,Del Lungo M,Jaconi M,Mugelli A,Cerbai E,Severi S

doi

10.1186/1475-925X-11-61

subject

Has Abstract

pub_date

2012-08-28 00:00:00

pages

61

issn

1475-925X

pii

1475-925X-11-61

journal_volume

11

pub_type

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