alpha-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 microm 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.
Department of Neurology and Paralyzed Veterans Association/Eastern Paralyzed Veterans Association Neuroscience Research Center, Yale Medical School, New Haven CT 06510, USA.
M
M
Renganathan
T R
TR
Cummins
W N
WN
Hormuzdiar
S G
SG
Waxman
D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D004553:Electric Conductivity; D005260:Female; D005456:Fluorescent Dyes; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009475:Neurons, Afferent / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012867:Skin / Q000294:innervation; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism*; D013266:Stilbamidines; D013779:Tetrodotoxin / Q000494:pharmacology*
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568318:Scn10a protein, mouse; D015222:Sodium Channels; D013266:Stilbamidines; D013779:Tetrodotoxin; D012964:Sodium