Effects of extracellular environments on development and differenciation of cardiac ion channels

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This study was aimed to investigate terminal differentiaiotn of cardiac progenitor cells in the early embryogenesis, and ionic currents development after birth in relation to exogenous influence. We heve already established culture systems of the mouse gastrula mesoderm and rat neonatal ventricular myocytes.Our study in early cardiogenesis indicates that at 7.5 days post coitum, when gastrulation is completed, mesodermal cardiac progenitor cells commit to autonomous differentiation into contractile cardiomyocytes, while 7.25 day post coitum mesoderm requires additional signaling for terminal differentiation. Insulin, insulin-like growth factor and platelet derived growth factor induced cardiomyocytes with spontaneous beating.In ionic current analysis of neonatal rat ventricular myocytes cultured for 5-15 days, development of ionic currents, especially of I_<to>, showed various patterns, which were dependent on culture states. Hypoxic culture condition retarded or dedifferentiated I_<to> development. Basic fibroblast growth factor enhanced development of I_<to>. Insulin-like growth factor increased the percentage of cells expressing I_<Kur>. In order to explore the molecular mechanism of developmental changes in ionic currents induced by culture condition, we are engaged in microinjection of the exogenous mRNA into cultured cardiomyocytes.The changes of culture condition, such as hypoxia and modification of culture medium, regulated the ion channels expression. Our findings suggest that environmental factors play important role in ionic channels development as well as in the early cardiogenesis.