a-SNS Produces the Slow TTX-Resistant Sodium Current in Large Cutaneous Afferent DRG Neurons

Renganathan, M., T. R. Cummins, W. N. Hormuzdiar, and S. G. Waxman. a-SNS produces the slow TTX-resistant sodium current in large cutaneous afferent DRG neurons. J Neurophysiol 84: 710–718, 2000. In this study, we used sensory neuron specific (SNS) sodium channel gene knockout (2/2) mice to ask whether SNS sodium channel produces the slow Na current (“slow”) in large (.40 mm diam) cutaneous afferent dorsal root ganglion (DRG) neurons. SNS wild-type (1/1) 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 (1/1) 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 6 0.12 and 0.39 6 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 (TTXR). Slow Na currents could not be detected in large cutaneous afferent neurons from SNS (2/2) mice; these cells expressed only fast Na current, and it was blocked by 300 nM TTX. The fast Na current density in SNS (2/2) neurons was 1.47 6 0.14 nA/pF, approximately 60% higher than the current density observed in SNS (1/1) 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 (1/1) or SNS (2/2) mice. These results show that the slow TTX-R Na current in large cutaneous afferent DRG is produced by the SNS sodium channel.