title: 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.
authors.affiliation: Biomedical Engineering Laboratory - D.E.I.S. University of Bologna, Via Venezia 52, Cesena, 47521, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Paci
authors.forename: Laura
authors.initials: L
authors.lastname: Sartiani
authors.forename: Martina
authors.initials: M
authors.lastname: Del Lungo
authors.forename: Marisa
authors.initials: M
authors.lastname: Jaconi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mugelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
authors.forename: Stefano
authors.initials: S
authors.lastname: Severi
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004553:Electric Conductivity; D053595:Embryonic Stem Cells / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D013997:Time Factors
chemical_list: D026902:Potassium Channel Blockers; D002118:Calcium