Nitric Oxide Is an Autocrine Regulator of Na+ Currents in Axotomized C-Type DRG Neurons

Department of Neurology, Yale Medical School, New Haven 06510; and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Neuroscience Research Center and Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut 06516 Renganathan, M., T. R. Cummins, W. N. Hormuzdiar, J. A. Black, and S. G. Waxman. Nitric Oxide Is an Autocrine Regulator of Na + Currents in Axotomized C-Type DRG Neurons. J. Neurophysiol. 83: 2431-2442, 2000. In this study, we examined whether nitric oxide synthase (NOS) is upregulated in small dorsal root ganglion (DRG) neurons after axotomy and, if so, whether the upregulation of NOS modulates Na + currents in these cells. We identified axotomized C-type DRG neurons using a fluorescent label, hydroxystilbamine methanesulfonate and found that sciatic nerve transection upregulates NOS activity in 60% of these neurons. Fast-inactivating tetrodotoxin-sensitive (TTX-S) Na + ("fast") current and slowly inactivating tetrodotoxin-resistant (TTX-R) Na + ("slow") current were present in control noninjured neurons with current densities of 1.08 ± 0.09 nA/pF and 1.03 ± 0.10 nA/pF, respectively (means ± SE). In some control neurons, a persistent TTX-R Na + current was observed with current amplitude as much as ~50% of the TTX-S Na + current amplitude and 100% of the TTX-R Na + current amplitude. Seven to 10 days after axotomy, current density of the fast and slow Na + currents was reduced to 0.58 ± 0.05 nA/pF ( P