A TTX-sensitive Inward Sodium Current Contributes to Spontaneous Activity in Newborn Rabbit Sino-atrial Node Cells

1. Single cells were isolated from the sinus node region of rabbits (2 days old to adult) to study the age-dependent contribution of the sodium current (iNa) to pacemaker activity. 2. Experiments were conducted in 50 mM Na(+)-Ca(2+)-free solution. All newborn cells (2-19 days) exhibited a TTX-sensitive, Mn(2+)-insensitive fast inward Na+ current (peak current density 115.5 +/- 11.9 pA pF-1 at 0 mV). Fifty per cent of young cells (20-40 days) possessed the current, but only one in ten adult cells. Current density decreased with development independently of cell capacitance. 3. Newborn cells exhibited a noticeable window current. With development, the position of the activation curve was shifted in the positive direction, while the inactivation was unaltered, resulting in reduced overlap of the two curves and hence less window current. 4. In newborn cells, 3 microM TTX significantly reduced all measured parameters of spontaneous action potentials, slowing rate by 63%. In contrast, there was no significant effect of TTX on rate or most of the same parameters in adult cells. 5. These results indicate that cells of the sinus node region exhibit a substantial TTX-sensitive current at birth. With development, both the density and frequency of occurrence of this current within the sinus node decrease, as does its contribution to automaticity.