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.
Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes / M. Paci; L. Sartiani; M. Del Lungo; M. Jaconi; A. Mugelli; E. Cerbai; S. Severi. - In: BIOMEDICAL ENGINEERING ONLINE. - ISSN 1475-925X. - ELETTRONICO. - 11:(2012), pp. 61.1-61.22. [10.1186/1475-925X-11-61]
Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes
PACI, MICHELANGELO;SEVERI, STEFANO
2012
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
