A TTX-SENSITIVE INWARD SODIUM CURRENT CONTRIBUTES TO SPONTANEOUS ACTIVITY IN NEWBORN RABBIT SINOATRIAL 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 sod ium current (i(Na)) to pacemaker activity 2. Experiments were conducte d in 50 mM Na+-Ca2+-free solution. All newborn cells (2-19 days) exhib ited a TTX-sensitive, Mn2+-insensitive fast inward Na+ current (peak c urrent density 115.5 +/- 11.9 pA pF(-1) at 0 mV). Fifty per cent of yo ung cells (20-40 days) possessed the current, but only one in ten adul t cells. Current density decreased with development independently of c ell capacitance. 3. Newborn cells exhibited a noticeable window curren t. With development, the position of the activation curve was shifted in the positive direction, while the inactivation was unaltered, resul ting in reduced overlap of the two curves and hence less window curren t. 4. In newborn cells, 3 mu M TTX significantly reduced all measured parameters of spontaneous action potentials, slowing rate by 63%. In c ontrast, there was no significant effect of TTX on rate or most of the same paramenters 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 occurren ce of this current within the sinus node decrease, as does its contrib ution to automaticity.