The TTX-resistant sodium channel Nav1.8 (SNS/PN3): expression and correlation with membrane properties in rat nociceptive primary afferent neurons.
We have examined the distribution of the sensory neuron-specific Na+ channel Nav1.8 (SNS/PN3) in nociceptive and non-nociceptive dorsal root ganglion (DRG) neurons and whether its distribution is related to neuronal membrane properties. Nav1.8-like immunoreactivity (Nav1.8-LI) was examined with an affinity purified polyclonal antiserum (SNS11) in rat DRG neurons that were classified according to sensory receptive properties and by conduction velocity (CV) as C-, Adelta- or Aalpha/beta. A significantly higher proportion of nociceptive than low threshold mechanoreceptive (LTM) neurons showed Nav1.8-LI, and nociceptive neurons had significantly more intense immunoreactivity in their somata than LTM neurons. Results showed that 89, 93 and 60% of C-, Adelta- and Aalpha/beta-fibre nociceptive units respectively and 88% of C-unresponsive units were positive. C-unresponsive units had electrical membrane properties similar to C-nociceptors and were considered to be nociceptive-type neurons. Weak positive Nav1.8-LI was also present in some LTM units including a C LTM, all Adelta LTM units (D hair), about 10% of cutaneous LTM Aalpha/beta-units, but no muscle spindle afferent units. Nav1.8-LI intensity was negatively correlated with soma size (all neurons) and with dorsal root CVs in A- but not C-fibre neurons. Nav1.8-LI intensity was positively correlated with action potential (AP) duration (both rise and fall time) in A-fibre neurons and with AP rise time only in positive C-fibre neurons. It was also positively correlated with AP overshoot in positive neurons. Thus high levels of Nav1.8 protein may contribute to the longer AP durations (especially in A-fibre neurons) and larger AP overshoots that are typical of nociceptors.
Djouhri
Laiche
L
Department of Physiology, University of Bristol Medical School, Bristol BS8 1TD, UK.
Fang
Xin
X
Okuse
Kenji
K
Wood
John N
JN
Berry
Carol M
CM
Lawson
Sally N
SN
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D048429:Cell Size; D004594:Electrophysiology; D005260:Female; D005456:Fluorescent Dyes; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D007150:Immunohistochemistry; D008465:Mechanoreceptors / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009413:Nerve Fibers, Myelinated / Q000502:physiology / Q000648:ultrastructure; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000187:drug effects; D009431:Neural Conduction; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D015222:Sodium Channels / Q000096:biosynthesis* / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology*
D005456:Fluorescent Dyes; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568319:Scn10a protein, rat; D015222:Sodium Channels; D013779:Tetrodotoxin