Differential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons

Brain Res Mol Brain Res. 1999 Apr 20;67(2):267-82. doi: 10.1016/s0169-328x(99)00070-4.


Following sciatic nerve transection, the electrophysiological properties of small dorsal root ganglion (DRG) neurons are markedly altered, with attenuation of TTX-R sodium currents and the appearance of rapidly repriming TTX-S currents. The reduction in TTX-R currents has been attributed to a down-regulation of sodium channels SNS/PN3 and NaN. While infusion of exogenous NGF to the transected nerve restores SNS/PN3 transcripts to near-normal levels in small DRG neurons, TTX-R sodium currents are only partially rescued. Binding of the isolectin IB4 distinguishes two subpopulations of small DRG neurons: IB4+ neurons, which express receptors for the GDNF family of neurotrophins, and IB4- neurons that predominantly express TrkA. We show here that SNS/PN3 is expressed in approximately one-half of both IB4+ and IB4- DRG neurons, while NaN is preferentially expressed in IB4+ neurons. Whole-cell patch-clamp studies demonstrate that TTX-R sodium currents in IB4+ neurons have a more hyperpolarized voltage-dependence of activation and inactivation than do IB4- neurons, suggesting different electrophysiological properties for SNS/PN3 and NaN. We confirm that NGF restores SNS/PN3 mRNA levels in DRG neurons in vitro and demonstrate that the trk antagonist K252a blocks this rescue. The down-regulation of NaN mRNA is, nevertheless, not rescued by NGF-treatment in either IB4+ or IB4- neurons and NGF-treatment in vitro does not significantly increase the peak amplitude of the TTX-R current in small DRG neurons. In contrast, GDNF-treatment causes a twofold increase in the peak amplitude of TTX-R sodium currents and restores both SNS/PN3 and NaN mRNA to near-normal levels in IB4+ neurons. These observations provide a mechanism for the partial restoration of TTX-R sodium currents by NGF in axotomized DRG neurons, and demonstrate that the neurotrophins NGF and GDNF differentially regulate sodium channels SNS/PN3 and NaN.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Axotomy
  • Cell Size / drug effects
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Down-Regulation / drug effects
  • Drug Resistance
  • Female
  • Ganglia, Spinal / chemistry
  • Ganglia, Spinal / cytology
  • Gene Expression / drug effects
  • Glial Cell Line-Derived Neurotrophic Factor
  • Lectins
  • Membrane Potentials / drug effects
  • NAV1.8 Voltage-Gated Sodium Channel
  • NAV1.9 Voltage-Gated Sodium Channel
  • Nerve Growth Factors / pharmacology*
  • Nerve Tissue Proteins / pharmacology*
  • Neurons, Afferent / chemistry*
  • Neurons, Afferent / physiology
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Patch-Clamp Techniques
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / cytology
  • Sciatic Nerve / physiology
  • Sodium Channels / genetics*
  • Sodium Channels / metabolism
  • Tetrodotoxin / pharmacology*
  • Up-Regulation / physiology


  • Gdnf protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Lectins
  • NAV1.8 Voltage-Gated Sodium Channel
  • NAV1.9 Voltage-Gated Sodium Channel
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neuropeptides
  • RNA, Messenger
  • Scn10a protein, rat
  • Scn11a protein, rat
  • Sodium Channels
  • Tetrodotoxin