Tetrodotoxin-sensitive Sodium Current in Rat Fetal Ventricular Myocytes - Contribution to the plateau phase of action potential

In cardiomyocytes of some animals, the Na+ current shows slow gating properties, and seems to contribute to the plateau phase of the action potential. In the present study, we characterized the fast Na+ current in freshly-isolated ventricular cardiomyocytes from 18-day-old fetal rats, using whole-cell patch clamp, and examined a possible contribution of the Na+ current to action potential duration (APD). Currents were recorded (at 25°C) in Ca2+-K+-free external and internal (pipette) solutions with 143 mM [Na]o and 20 mM [Na]i. The fast Na+ current was elicited by depolarizing steps above -47 mV from a holding potential of -97 mV. The maximal amplitude of the current was 735 ± 94 pA (mean ± S.E., n = 11) at -7 mV. The current density was 39.0 ± 6.7 pA/pF (n = 9). The reversal potential was 51 ± 3 mV (n = 11), agreeing with the equilibrium potential for Na+ (51 mV). The inward current was completely blocked in absence of [Na]o and by tetrodotoxin (TTX, 10 μM). The inactivation curve (h∞) was sigmoidal between -127 and -27 mV, the half-inactivation potential and slope factor (k) being -69 and 9.5 mV, respectively. The activation curve (normalized gNa) was also sigmoidal, with half-activation voltage and k of -27 mV and -8.4 mV, respectively. The two curves overlapped from -60 to -30 mV. The current decay was best fitted by a two-exponential equation: (a) the time constant of the fast component (τif) decreased from 3.9 ± 0.6 ms at -37 mV to 0.8 ± 0.1 ms at 23 mV; (b) the slow component (τis) declined from 31 ± 8 ms to 16 ± 3 ms at the same potentials. The recovery from inactivation has also two components: fast (τif = 10 ± 2 ms) and slow (τis = 307 ± 44 ms). TTX (1 μM) decreased the slow inactivating component and ADP50 by 69.5 ± 4.2% and 25 ± 6%, respectively. Therefore, the Na+ current in rat fetal cardiomyocytes may significantly contribute to the plateau phase of the action potential. The kinetics properties of the fast Na+ current of the 18-day fetal cardiomyocytes were compared with those from 1-day old neonatal rats. The current density was lower and the current decay was slower in the fetal cells in comparison with neonatal cells.