Differential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons - PubMed (original) (raw)
Differential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons
J Fjell et al. Brain Res Mol Brain Res. 1999.
Free article
Abstract
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.
Copyright 1999 Elsevier Science B.V.
Similar articles
- Glial-derived neurotrophic factor upregulates expression of functional SNS and NaN sodium channels and their currents in axotomized dorsal root ganglion neurons.
Cummins TR, Black JA, Dib-Hajj SD, Waxman SG. Cummins TR, et al. J Neurosci. 2000 Dec 1;20(23):8754-61. doi: 10.1523/JNEUROSCI.20-23-08754.2000. J Neurosci. 2000. PMID: 11102483 Free PMC article. - Rescue of alpha-SNS sodium channel expression in small dorsal root ganglion neurons after axotomy by nerve growth factor in vivo.
Dib-Hajj SD, Black JA, Cummins TR, Kenney AM, Kocsis JD, Waxman SG. Dib-Hajj SD, et al. J Neurophysiol. 1998 May;79(5):2668-76. doi: 10.1152/jn.1998.79.5.2668. J Neurophysiol. 1998. PMID: 9582237 - Changes in expression of two tetrodotoxin-resistant sodium channels and their currents in dorsal root ganglion neurons after sciatic nerve injury but not rhizotomy.
Sleeper AA, Cummins TR, Dib-Hajj SD, Hormuzdiar W, Tyrrell L, Waxman SG, Black JA. Sleeper AA, et al. J Neurosci. 2000 Oct 1;20(19):7279-89. doi: 10.1523/JNEUROSCI.20-19-07279.2000. J Neurosci. 2000. PMID: 11007885 Free PMC article. - Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuropathic conditions.
Novakovic SD, Tzoumaka E, McGivern JG, Haraguchi M, Sangameswaran L, Gogas KR, Eglen RM, Hunter JC. Novakovic SD, et al. J Neurosci. 1998 Mar 15;18(6):2174-87. doi: 10.1523/JNEUROSCI.18-06-02174.1998. J Neurosci. 1998. PMID: 9482802 Free PMC article. Review. - [The role of tetrodotoxin-resistant sodium channels in pain sensation studied on sns-knockout mice].
Ogata N, Yamamoto M, Maruyama H. Ogata N, et al. Nihon Rinsho. 2001 Sep;59(9):1688-97. Nihon Rinsho. 2001. PMID: 11554037 Review. Japanese.
Cited by
- Mouse DRG Cell Line with Properties of Nociceptors.
Doran C, Chetrit J, Holley MC, Grundy D, Nassar MA. Doran C, et al. PLoS One. 2015 Jun 8;10(6):e0128670. doi: 10.1371/journal.pone.0128670. eCollection 2015. PLoS One. 2015. PMID: 26053673 Free PMC article. - Human Na(v)1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons.
Han C, Estacion M, Huang J, Vasylyev D, Zhao P, Dib-Hajj SD, Waxman SG. Han C, et al. J Neurophysiol. 2015 May 1;113(9):3172-85. doi: 10.1152/jn.00113.2015. Epub 2015 Mar 18. J Neurophysiol. 2015. PMID: 25787950 Free PMC article. - Neurotrophins and Neuropathic Pain: Role in Pathobiology.
Khan N, Smith MT. Khan N, et al. Molecules. 2015 Jun 9;20(6):10657-88. doi: 10.3390/molecules200610657. Molecules. 2015. PMID: 26065639 Free PMC article. Review. - GTP gamma S increases Nav1.8 current in small-diameter dorsal root ganglia neurons.
Saab CY, Cummins TR, Waxman SG. Saab CY, et al. Exp Brain Res. 2003 Oct;152(4):415-9. doi: 10.1007/s00221-003-1565-7. Epub 2003 Jul 24. Exp Brain Res. 2003. PMID: 12898089 - Transfection of rat or mouse neurons by biolistics or electroporation.
Dib-Hajj SD, Choi JS, Macala LJ, Tyrrell L, Black JA, Cummins TR, Waxman SG. Dib-Hajj SD, et al. Nat Protoc. 2009;4(8):1118-26. doi: 10.1038/nprot.2009.90. Epub 2009 Jul 9. Nat Protoc. 2009. PMID: 19617884
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources