title: Contribution of quantitative changes in individual ionic current systems to the embryonic development of ventricular myocytes: a simulation study.
abstract: Early embryonic rodent ventricular cells exhibit spontaneous action potential (AP), which disappears in later developmental stages. Here, we used 3 mathematical models-the Kyoto, Ten Tusscher-Panfilov, and Luo-Rudy models-to present an overview of the functional landscape of developmental changes in embryonic ventricular cells. We switched the relative current densities of 9 ionic components in the Kyoto model, and 160 of 512 representative combinations were predicted to result in regular spontaneous APs, in which the quantitative changes in Na(+) current (I Na) and funny current (I f) made large contributions to a wide range of basic cycle lengths. In all three models, the increase in inward rectifier current (I K1) before the disappearance of I f was predicted to result in abnormally high intracellular Ca(2+) concentrations. Thus, we demonstrated that the developmental changes in APs were well represented, as I Na increased before the disappearance of I f, followed by a 10-fold increase in I K1.
authors.affiliation: Institute for Advanced Biosciences, Keio University, Fujisawa, Kanagawa 252-0882, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Okubo
authors.forename: Hitomi I
authors.initials: HI
authors.lastname: Sano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Naito
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003198:Computer Simulation; D047108:Embryonic Development / Q000502:physiology; D006321:Heart / Q000196:embryology* / Q000502:physiology; D006352:Heart Ventricles / Q000196:embryology / Q000378:metabolism; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D012964:Sodium / Q000378:metabolism
chemical_list: D012964:Sodium; D002118:Calcium