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 < 0.01) and 0.2 ± 0.05 nA/pF (P < 0.001), respectively. Persistent TTX-R Na+ current was not observed in axotomized neurons. Nitric oxide (NO) produced by the upregulation of NOS can block Na+ currents. To examine the role of NOS upregulation on the reduction of the three types of Na+ currents in axotomized neurons, axotomized DRG neurons were incubated with 1 mM N(G)- nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. The current density of fast and slow Na+ channels in these neurons increased to 0.82 ± 0.08 nA/pF (P < 0.01) and 0.34 ± 0.04 nA/pF (P < 0.05), respectively. However, we did not observe any persistent TTX-R current in axotomized neurons incubated with L-NAME. These results demonstrate that endogenous 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+ currents in injured DRG neurons.
|Original language||English (US)|
|Number of pages||12|
|Journal||Journal of Neurophysiology|
|State||Published - Apr 20 2000|
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