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

M. Renganathan, Theodore Cummins, W. N. Hormuzdiar, J. A. Black, S. G. Waxman

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Abstract

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 languageEnglish
Pages (from-to)2431-2442
Number of pages12
JournalJournal of Neurophysiology
Volume83
Issue number4
StatePublished - 2000
Externally publishedYes

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Spinal Ganglia
Nitric Oxide
Neurons
Tetrodotoxin
Nitric Oxide Synthase
NG-Nitroarginine Methyl Ester
Up-Regulation
Axotomy
Sciatic Nerve

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Renganathan, M., Cummins, T., Hormuzdiar, W. N., Black, J. A., & Waxman, S. G. (2000). Nitric oxide is an autocrine regulator of Na+ currents in axotomized C- type DRG neurons. Journal of Neurophysiology, 83(4), 2431-2442.

Nitric oxide is an autocrine regulator of Na+ currents in axotomized C- type DRG neurons. / Renganathan, M.; Cummins, Theodore; Hormuzdiar, W. N.; Black, J. A.; Waxman, S. G.

In: Journal of Neurophysiology, Vol. 83, No. 4, 2000, p. 2431-2442.

Research output: Contribution to journalArticle

Renganathan, M, Cummins, T, Hormuzdiar, WN, Black, JA & Waxman, SG 2000, 'Nitric oxide is an autocrine regulator of Na+ currents in axotomized C- type DRG neurons', Journal of Neurophysiology, vol. 83, no. 4, pp. 2431-2442.
Renganathan, M. ; Cummins, Theodore ; Hormuzdiar, W. N. ; Black, J. A. ; Waxman, S. G. / Nitric oxide is an autocrine regulator of Na+ currents in axotomized C- type DRG neurons. In: Journal of Neurophysiology. 2000 ; Vol. 83, No. 4. pp. 2431-2442.
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N2 - 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.

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