Nitric oxide is an autocrine regulator of Na+ currents in axotomized C-type DRG neurons

Nitric oxide is an autocrine regulator of Na+ currents in axotomized C-type DRG neurons. J. Neurophhsiol. 83: 2431-2442, 2000. In this study, we exami ned 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-ty pe DRG neurons using a fluorescent label, hydroxystilbamine methanesulfonat e and found that sciatic nerve transection upregulates NOS activity in 60% of these neurons. Fast-inactivating tetrodotoxin-sensitive (TTX-S) Na+ ("fa st") current and slowly inactivating terrodotoxin-resistant (TTX-R) Na+ ("s low") current were present in control noninjured neurons with current densi ties of 1.08 +/- 0.09 nA/pF and 1.03 +/- 0.10 nA/pF, respectively (means I SE). In some control neurons, a persistent TTX-R Na+ current was observed w ith current amplitude as much as similar to 50% of the TTX-S Na+ current am plitude 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 < 0.01) and 0.2 +/- 0.05 nA/pF (P < 0.001), respecti vely. Persistent TTX-R Na+ current was not observed in axotomized neurons. Nitric oxide (NO) produced by the upregulation of NOS can block Na+ current s. To examine the role of NOS upregulation on the. reduction of the three t ypes of Na+ currents in axotomized neurons, axotomized DRG neurons were inc ubated with 1 mM N-G-nitro-L-arginine methyl ester (L-NAME), a NOS inhibito r. The current density of fast and slow Na+ channels in these neurons incre ased to 0.82 +/- 0.08 nA/pF (P < 0.01) and 0.34 +/- 0.04 nAl/F (P < 0.05), respectively, However, we did not observe any persistent TTX-R current in a xotomized neurons incubated with L-NAME. These results: demonstrate that en dogenous NO/NO-related species block both fast and slow Na+ current in DRG neurons and suggest that NO functions as an autocrine regulator of Na+ curr ents in injured DRG neurons.