A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons

TTX-resistant (TTX-R) sodium currents are preferentially expressed in small C-type dorsal root ganglion (DRG) neurons, which include nociceptive neuro ns. Two mRNAs that are predicted to encode TTX-R sodium channels, SNS and N aN, are preferentially expressed in C-type DRG cells. To determine whether there are multiple TTX-R currents in these cells, we used patch-clamp recor dings to study sodium currents in SNS-null mice and found a novel persisten t voltage-dependent sodium current in small DRG neurons of both SNS-null an d wild-type mice. Like SNS currents, this current is highly resistant to TT X (K-i = 39 +/- 9 mu M). In contrast to SNS currents, the threshold for act ivation of this current is near -70 mV, the midpoint of steady-state inacti vation is -44 +/- 1 mV, and the time constant for inactivation is 43 +/- 4 msec at -20 mV. The presence of this current in SNS-null and wild-type mice demonstrates that a distinct sodium channel isoform, which we suggest to b e NaN, underlies this persistent TTX-R current. Importantly, the hyperpolar ized voltage-dependence of this current, the substantial overlap of its act ivation and steady-state inactivation curves and its persistent nature sugg est that this current is active near resting potential, where it may play a n important role in regulating excitability of primary sensory neurons.