α-SNS produces the slow TTX-resistant sodium current in large cutaneous afferent DRG neurons

In this study, we used sensory neuron specific (SNS) sodium channel gene knockout (-/-) mice to ask whether SNS sodium channel produces the slow Na+ current ("slow") in large (>40 mu m diam) cutaneous afferent dorsal root ganglion (DRG) neurons. SNS wild-type (+/+) mice were used as controls. Retrograde Fluoro-Gold labeling permitted the definitive identification of cutaneous afferent neurons. Prepulse inactivation was used to separate the fast and slow Na+ currents. Fifty-two percent of the large cutaneous afferent neurons isolated from SNS (+/+) mice expressed only fast-inactivating Na+ currents ("fast"), and 48% expressed both fast and slow Na+ currents. The fast and slow current densities were 0.90 +/- 0.12 and 0.39 +/- 0.16 nA/pF, respectively. Fast Na+ currents were blocked completely by 300 nM tetrodotoxin (TTX), while slow Na+ currents were resistant to 300 nM TTX, confirming that the slow Na+ currents observed in large cutaneous DRG neurons are TTX-resistant (TTX-R). Slow Na+ currents could not be detected in large cutaneous afferent neurons from SNS (-/-) mice; these cells expressed only fast Na+ current, and it was blocked by 300 nM TTX. The fast Na+ current density in SNS (-/-) neurons was 1.47 +/- 0.14 nA/pF, approximately 60% higher than the current density observed in SNS (+/+) mice (P < 0.02). A low-voltage-activated TTX-R Na+ current ("persistent") observed in small C-type neurons is not present in large cutaneous afferent neurons from either SNS (+/+) or SNS (-/-) mice. These results show that the slow TTX-R Na+ current in large cutaneous afferent DRG is produced by the SNS sodium channel.