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J Physiol Sci. 2013 Sep;63(5):355-67. doi: 10.1007/s12576-013-0271-x. Epub 2013 Jun 13.

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

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Institute for Advanced Biosciences, Keio University, Fujisawa, Kanagawa 252-0882, Japan.


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.

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