Upregulation of a silent sodium channel after peripheral, but not central,nerve injury in DRG neurons

After transection of their axons within the sciatic nerve, DRG neurons beco me hyperexcitable. Recent studies have demonstrated the emergence of a rapi dly repriming tetrodotoxin (TTX)-sensitive sodium current that may account for this hyperexcitability in axotomized small (<27 mu m diam) DRG neurons, but its molecular basis has remained unexplained. It has been shown previo usly that sciatic nerve transection leads to an upregulation of sodium chan nel III transcripts, which normally are present at very low levels in DRG n eurons, in adult rats. We show here that TTX-sensitive currents in small DR G neurons, after transection of their peripheral axonal projections, reprim e more rapidly than those in control neurons throughout a voltage range of -140 to -60 mV, a finding that suggests that these currents are produced by a different sodium channel. After transection of the central axonal projec tions (dorsal rhizotomy) of these small DRG neurons, in contrast, the repri ming kinetics of TTX-sensitive sodium currents remain similar to those of c ontrol (uninjured) neurons. We also demonstrate, with two distinct antibodi es directed against different regions of the type III sodium channel, that small DRG neurons display increased brain type III immunostaining when stud ied 7-12 days after transection of their peripheral, but not central, proje ctions. Type III sodium channel immunoreactivity is present within somata a nd neurites of peripherally axotomized, but not centrally axotomized, neuro ns studied after <24 h in vitro. Peripherally axotomized DRG neurons in sit u also exhibit enhanced type III staining compared with control neurons, in cluding an accumulation of type III sodium channels in the distal portion o f the ligated and transected sciatic nerve, but these changes are not seen in centrally axotomized neurons. These observations are consistent with a c ontribution of type III sodium channels to the rapidly repriming sodium cur rents observed in peripherally axotomized DRG neurons and suggest that type III channels may at least partially account for the hyperexcitibility of t hese neurons after injury.