NGF has opposing effects on Na+ channel III and SNS gene expression in spinal sensory neurons.
Following sciatic nerve transection, the expression of sodium channel III (alpha-III) transcripts increases and SNS (alpha-SNS) transcripts decreases in small (< 25 microns diameter) dorsal root ganglion (DRG) neurons, which may reflect an interruption of retrograde transport of peripherally derived factor(s) involved in the regulation of these channels. To test the hypothesis that the neurotrophin nerve growth factor (NGF), which is abundant in peripheral targets, participates in the modulation of the expression of these sodium channel transcripts, we examined the hybridization signal of alpha-SNS and alpha-III mRNAs in small DRG neurons from adult rats that had been dissociated and maintained for 7 days in the absence or presence of exogenous NGF. Neurons maintained in control (no added NGF) cultures showed changes in alpha-III and alpha-SNS hybridization signal similar to those induced by axotomy, with increased alpha-III mRNA levels and decreased alpha-SNS mRNA levels, compared with those observed in small DRG neurons at 1 day in vitro. The addition of exogenous NGF to DRG cultures attenuated these alterations in transcript levels, decreasing alpha-III mRNA and increasing alpha-SNS mRNA expression. These results suggest that NGF participates in the regulation of membrane excitability in small DRG neurons by pathways that include opposing effects on different sodium channel genes.
Black
J A
JA
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Langworthy
K
K
Hinson
A W
AW
Dib-Hajj
S D
SD
Waxman
S G
SG
D000818:Animals; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D007150:Immunohistochemistry; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
D062559:NAV1.8 Voltage-Gated Sodium Channel; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C568319:Scn10a protein, rat; D015222:Sodium Channels