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 Onlinejournal_title
Biomedical engineering onlineauthors
Paci M,Sartiani L,Del Lungo M,Jaconi M,Mugelli A,Cerbai E,Severi Sdoi
10.1186/1475-925X-11-61subject
Has Abstractpub_date
2012-08-28 00:00:00pages
61issn
1475-925Xpii
1475-925X-11-61journal_volume
11pub_type
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