Molecular and Functional Changes in Voltage-Gated Na+ Channels in Cardiomyocytes During Mouse Embryogenesis

Background: Embryonic cardiomyocytes undergo profound changes in their electrophysiological properties during development. However, the molecular and functional changes in Na+ channel during cardiogenesis are not yet fully explained. Methods and Results: To study the functional changes in the Na+ channel during cardiogenesis, Na+ currents were recorded in the early (EDS) and late (LDS) developmental stages of cardiomyocytes in embryonic mice. Compared with EDS myocytes, LDS myocytes exhibited a larger peak current density, a more negative shift in the voltage of half inactivation, a larger fast inactivation component and a smaller slow inactivation component, and smaller time constants for recovery from inactivation. Additionally, multiple Na+ channel alpha-subunits (Nay 1.1-1.6) and beta-subunits (Nay beta 1-beta 3) of mouse embryos were investigated. Transcripts of Nay 1.1-1.3 were absent or present at very low levels in embryonic hearts. Transcripts encoding Nay 1.4-1.6 and Nay beta 1-beta 3 increased during embryogenesis. Data on the sensitivity of total Na+ currents to tetrodotoxin (TTX) showed that TTX-resistant Nay 1.5 is the predominant isoform expressed in the heart of the mouse embryo. Conclusions: The results indicate that significant changes in the functional properties of Na+ channels develop in the cardiomyocytes of the mouse embryo, and that different Na+ channel subunit genes are strongly regulated during embryogenesis, which further support a physiological role for voltage-gated Na+ channels during heart development. (Circ J 2011; 75: 2071-2079)