Role of sodium channels in the spontaneous excitability of early embryonic cardiomyocytes.

Sodium channels play an important role in action potentials. Moreover, some evidences recently suggested that sodium channels were responsible for murine sinoatrial node pacemaking. The aim of this study was to investigate the role of sodium channels in pacemaking in embryonic cardiomyocytes in early development stage (EDS). Whole-cell patch-clamp technique was employed to record sodium current of murine early embryonic cardiomyocytes. Current clamp technique was used to record the effect of 0.1, 1 and 10 μM tetrodotoxin (TTX) on embryonic cardiomyocytes pacemaking. Electro- physiology properties of sodium channels in embryonic cardiomyocytes corresponded to Nav1.5, and the IC₅₀ of TTX was 5.24 μM. TTX at 0.1 μM concentration had no effects on the pacemaking. TTX at 1 μM concentration, however, dramatically slowed the spontaneous beating rate from 73.975 ± 10.478 to 50.268 ± 10.476 cycle/min (P < 0.05), and the maximum upstroke velocity (dV/dtmax) of phase 4 from 0.074 ± 0.006 to 0.046 ± 0.007 V/s (P < 0.01). Furthermore, 1 μM TTX reduced the dV/dtmax of phase 0 from 16.405 ± 0.056 to 12.801 ± 0.084 V/s (P < 0.01), and increased the period of phase 4 from 710.342 ± 110.983 to 1320.618 ± 250.483 ms (P < 0.05). TTX at 1 μM also had some effects on the peak of phase 0 decreasing it from 40.621 ± 3.012 to 37.407 ± 2.749 mV (P < 0.05). But TTX at 1 μM had no effects on the period of phase 0. In some cells (9/13), TTX at 10 μM caused complete cessation of spontaneous action potentials. Our results suggested that the main expression subtype of sodium channels was Nav1.5 of early embryonic cardiomyocytes. And TTX-resistant sodium channels contributed to the initiation of action potentials of early embryonic cardiomyocytes, while TTX-sensitive sodium channels were not involved in initiation of action potentials.