The presence and role of the tetrodotoxin-resistant sodium channel Na(v)1.9 (NaN) in nociceptive primary afferent neurons.
This is the first examination of sensory receptive properties and associated electrophysiological properties in vivo of dorsal root ganglion (DRG) neurons that express the TTX-resistant sodium channel Na(v)1.9 (NaN). Intracellular recordings in lumbar DRGs in Wistar rats enabled units with dorsal root C-, Adelta-, or Aalpha/beta-fibers to be classified as nociceptive, low-threshold mechanoreceptive (LTM), or unresponsive. Intracellular dye injection enabled subsequent immunocytochemistry for Na(v)1.9-like immunoreactivity (Na(v)1.9-LI). Na(v)1.9-LI was expressed selectively in nociceptive-type (C- and A-fiber nociceptive and C-unresponsive) units. Of the nociceptive units, 64, 54, and 31% of C-, Adelta-, and Aalpha/beta-fiber units, respectively, were positive for Na(v)1.9-LI. C-unresponsive units were included in the nociceptive-type group on the basis of their nociceptor-like membrane properties; 91% were positive. Na(v)1.9-LI was undetectable in Adelta- or Aalpha/beta-fiber LTM units and in one C-LTM unit. Na(v)1.9-LI intensity was correlated negatively with soma size and conduction velocity in nociceptive units and with conduction velocity in C-fiber units. There was a positive correlation with action potential rise time in nociceptive-type units with membrane potentials equal to or more negative than -50 mV. The data provide direct evidence that Na(v)1.9 is expressed selectively in (but not in all) C- and A-fiber nociceptive-type units and suggest that Na(v)1.9 contributes to membrane properties that are typical of nociceptive neurons.
Department of Physiology, University of Bristol, Medical School, Bristol BS8 1TD, United Kingdom.
Xin
X
Fang
Laiche
L
Djouhri
Joel A
JA
Black
Sulayman D
SD
Dib-Hajj
Stephen G
SG
Waxman
Sally N
SN
Lawson
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009412:Nerve Fibers / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D009475:Neurons, Afferent / Q000145:classification / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C113705:Scn11a protein, rat; D015222:Sodium Channels; D013779:Tetrodotoxin