M. Renganathan et al., alpha-SNS produces the slow TTX-resistant sodium current in large cutaneous afferent DRG neurons, J NEUROPHYS, 84(2), 2000, pp. 710-718
In this study, we used sensory neuron specific (SNS) sodium channel gene kn
ockout (-/-) mice to ask whether SNS sodium channel produces the slow Na+ c
urrent ("slow") in large (>40 mu m diam) cutaneous afferent dorsal root gan
glion (DRG) neurons. SNS wild-type (+/+) mice were used as controls. Retrog
rade Fluoro-Gold labeling permitted the definitive identification of cutane
ous afferent neurons. Prepulse inactivation was used to separate the fast a
nd slow Na+ currents. Fifty-two percent of the large cutaneous afferent neu
rons isolated from SNS (+/+) mice expressed only fast-inactivating Na+ curr
ents ("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, resp
ectively. Fast Na+ currents were blocked completely by 300 nM tetrodotoxin
(TTX), while slow Na+ currents were resistant to 300 nM TTX, confirming tha
t the slow Na+ currents observed in large cutaneous DRG neurons are TTX-res
istant (TTX-R). Slow Na+ currents could not be detected in large cutaneous
afferent neurons from SNS (-/-) mice; these cells expressed only fast Na+ c
urrent, and it was blocked by 300 nM TTX. The fast Na+ current density in S
NS (-/-) 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-activ
ated TTX-R Na+ current ("persistent") observed in small C-type neurons is n
ot present in large cutaneous afferent neurons from either SNS (+/+) or SNS
(-/-) mice. These results show that the slow TTX-R Na+ current in large cu
taneous afferent DRG is produced by the SNS sodium channel.