M. Renganathan et al., Nitric oxide is an autocrine regulator of Na+ currents in axotomized C-type DRG neurons, J NEUROPHYS, 83(4), 2000, pp. 2431-2442
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.