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 degrees C) in Ca(2+)-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 microns). The inactivation curve (h infinity) 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 (tau if) decreased from 3.9 +/- 0.6 ms at -37 mV to 0.8 +/- 0.1 ms at 23 mV; (b) the slow component (tau is) declined from 31 +/- 8 ms to 16 +/- ms at the same potentials. The recovery from inactivation had also two components: fast (tau rf = 10 +/- 2 ms) and slow (tau rs = 307 +/- 44 ms). TTX (1 micron) 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.
Department of Physiology and Biophysics, College of Medicine, University of Cincinnati, Ohio 45267.
L
L
Conforti
N
N
Tohse
N
N
Sperelakis
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology*
D015222:Sodium Channels; D013779:Tetrodotoxin