Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons

J Comp Neurol. 2008 Sep 10;510(2):188-206. doi: 10.1002/cne.21786.

Abstract

We compared the distribution of the alpha-subunit mRNAs of voltage-gated sodium channels Nav1.1-1.3 and Nav1.6-1.9 and a related channel, Nax, in histochemically identified neuronal subpopulations of the rat dorsal root ganglia (DRG). In the naïve DRG, the expression of Nav1.1 and Nav1.6 was restricted to A-fiber neurons, and they were preferentially expressed by TrkC neurons, suggesting that proprioceptive neurons possess these channels. Nav1.7, -1.8, and -1.9 mRNAs were more abundant in C-fiber neurons compared with A-fiber ones. Nax was evenly expressed in both populations. Although Nav1.8 and -1.9 were preferentially expressed by TrkA neurons, other alpha-subunits were expressed independently of TrkA expression. Actually, all IB4(+) neurons expressed both Nav1.8 and -1.9, and relatively limited subpopulations of IB4(+) neurons (3% and 12%, respectively) expressed Nav1.1 and/or Nav1.6. These findings provide useful information in interpreting the electrophysiological characteristics of some neuronal subpopulations of naïve DRG. After L5 spinal nerve ligation, Nav1.3 mRNA was up-regulated mainly in A-fiber neurons in the ipsilateral L5 DRG. Although previous studies demonstrated that nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF) reversed this up-regulation, the Nav1.3 induction was independent of either TrkA or GFRalpha1 expression, suggesting that the induction of Nav1.3 may be one of the common responses of axotomized DRG neurons without a direct relationship to NGF/GDNF supply.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Size
  • Ganglia, Spinal* / cytology
  • Ganglia, Spinal* / metabolism
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / genetics
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
  • Horseradish Peroxidase / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Molecular Sequence Data
  • Neurofilament Proteins / genetics
  • Neurofilament Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Receptor, trkA / metabolism
  • Receptor, trkC / metabolism
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*

Substances

  • Gfra1 protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Neurofilament Proteins
  • Protein Isoforms
  • RNA, Messenger
  • Sodium Channels
  • neurofilament protein H
  • Horseradish Peroxidase
  • Receptor, trkA
  • Receptor, trkC