Contribution of quantitative changes in individual ionic current systems to the embryonic development of ventricular myocytes: a simulation study

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). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12576-013-0271-x) contains supplementary material, which is available to authorized users.