Molecular and functional changes in voltage-gated Na⁺ channels in cardiomyocytes during mouse embryogenesis

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.

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 α-subunits (Nav 1.1-1.6) and β-subunits (Nav β1-β3) of mouse embryos were investigated. Transcripts of Nav 1.1-1.3 were absent or present at very low levels in embryonic hearts. Transcripts encoding Nav 1.4-1.6 and Nav β1-β3 increased during embryogenesis. Data on the sensitivity of total Na⁺ currents to tetrodotoxin (TTX) showed that TTX-resistant Nav 1.5 is the predominant isoform expressed in the heart of the mouse embryo.

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.