The TTX-resistant sodium channel Nav1.8 (SNS/PN3): expression and correlation with membrane properties in rat nociceptive primary afferent neurons

J Physiol. 2003 Aug 1;550(Pt 3):739-52. doi: 10.1113/jphysiol.2003.042127. Epub 2003 Jun 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Blotting, Western
  • Cell Size
  • Electrophysiology
  • Female
  • Fluorescent Dyes
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / physiology
  • Immunohistochemistry
  • Mechanoreceptors / physiology
  • Membrane Potentials / physiology
  • NAV1.8 Voltage-Gated Sodium Channel
  • Nerve Fibers, Myelinated / physiology
  • Nerve Fibers, Myelinated / ultrastructure
  • Nerve Fibers, Unmyelinated / physiology
  • Nerve Fibers, Unmyelinated / ultrastructure
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / drug effects
  • Neural Conduction
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology*
  • Nociceptors / drug effects
  • Nociceptors / physiology*
  • Patch-Clamp Techniques
  • Rats
  • Sodium Channels / biosynthesis*
  • Sodium Channels / drug effects
  • Tetrodotoxin / pharmacology*

Substances

  • Fluorescent Dyes
  • NAV1.8 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • Scn10a protein, rat
  • Sodium Channels
  • Tetrodotoxin