Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury

Theodore Cummins, Stephen G. Waxman

Research output: Contribution to journalArticle

455 Citations (Scopus)

Abstract

Clinical and experimental studies have shown that spinal sensory neurons become hyperexcitable after axonal injury, and electrophysiological changes have suggested that this may be attributable to changes in sodium current expression. We have demonstrated previously that sodium channel α-III mRNA levels are elevated and sodium channel α-SNS mRNA levels are reduced in rat spinal sensory neurons after axotomy. In this study we show that small (C- type) rat spinal sensory neurons express sodium currents with dramatically different kinetics after axotomy produced by sciatic nerve ligation. Uninjured C-type neurons express both slowly inactivating tetrodotoxin- resistant (TTX-R) sodium current and a fast-inactivating tetrodotoxin- sensitive (TTx-S) current that reprimes (recovers from inactivation) slowly. After axotomy, the TTX-R current density was greatly reduced. No difference was observed in the density of TTX-S currents after axotomy, and their voltage dependence was not different from controls. However, TTX-S currents in axotomized neurons reprimed four times faster than control TTX-S currents. These data indicate that axotomy of spinal neurons is followed by downregulation of TTX-R current and by the emergence of a rapidly repriming TTX-S current and suggest that this may be attributable to the upregulation of a sodium channel isoform that was unexpressed previously in these cells. These axotomy-induced changes in sodium currents are expected to alter excitability substantially and could underlie the molecular pathogenesis of some chronic pain syndromes associated with injury to the axons of spinal sensory neurons.

Original languageEnglish (US)
Pages (from-to)3503-3514
Number of pages12
JournalJournal of Neuroscience
Volume17
Issue number10
StatePublished - 1997
Externally publishedYes

Fingerprint

Axotomy
Tetrodotoxin
Sensory Receptor Cells
Up-Regulation
Down-Regulation
Sodium
Sodium Channels
Wounds and Injuries
Neurons
Messenger RNA
Sciatic Nerve
Chronic Pain
Ligation
Axons
Protein Isoforms

Keywords

  • axotomy
  • chronic pain
  • dorsal root ganglion
  • excitability
  • sodium channel
  • sodium current

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{6687d3d4f6164b91a11cfed83ab59d58,
title = "Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury",
abstract = "Clinical and experimental studies have shown that spinal sensory neurons become hyperexcitable after axonal injury, and electrophysiological changes have suggested that this may be attributable to changes in sodium current expression. We have demonstrated previously that sodium channel α-III mRNA levels are elevated and sodium channel α-SNS mRNA levels are reduced in rat spinal sensory neurons after axotomy. In this study we show that small (C- type) rat spinal sensory neurons express sodium currents with dramatically different kinetics after axotomy produced by sciatic nerve ligation. Uninjured C-type neurons express both slowly inactivating tetrodotoxin- resistant (TTX-R) sodium current and a fast-inactivating tetrodotoxin- sensitive (TTx-S) current that reprimes (recovers from inactivation) slowly. After axotomy, the TTX-R current density was greatly reduced. No difference was observed in the density of TTX-S currents after axotomy, and their voltage dependence was not different from controls. However, TTX-S currents in axotomized neurons reprimed four times faster than control TTX-S currents. These data indicate that axotomy of spinal neurons is followed by downregulation of TTX-R current and by the emergence of a rapidly repriming TTX-S current and suggest that this may be attributable to the upregulation of a sodium channel isoform that was unexpressed previously in these cells. These axotomy-induced changes in sodium currents are expected to alter excitability substantially and could underlie the molecular pathogenesis of some chronic pain syndromes associated with injury to the axons of spinal sensory neurons.",
keywords = "axotomy, chronic pain, dorsal root ganglion, excitability, sodium channel, sodium current",
author = "Theodore Cummins and Waxman, {Stephen G.}",
year = "1997",
language = "English (US)",
volume = "17",
pages = "3503--3514",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "10",

}

TY - JOUR

T1 - Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury

AU - Cummins, Theodore

AU - Waxman, Stephen G.

PY - 1997

Y1 - 1997

N2 - Clinical and experimental studies have shown that spinal sensory neurons become hyperexcitable after axonal injury, and electrophysiological changes have suggested that this may be attributable to changes in sodium current expression. We have demonstrated previously that sodium channel α-III mRNA levels are elevated and sodium channel α-SNS mRNA levels are reduced in rat spinal sensory neurons after axotomy. In this study we show that small (C- type) rat spinal sensory neurons express sodium currents with dramatically different kinetics after axotomy produced by sciatic nerve ligation. Uninjured C-type neurons express both slowly inactivating tetrodotoxin- resistant (TTX-R) sodium current and a fast-inactivating tetrodotoxin- sensitive (TTx-S) current that reprimes (recovers from inactivation) slowly. After axotomy, the TTX-R current density was greatly reduced. No difference was observed in the density of TTX-S currents after axotomy, and their voltage dependence was not different from controls. However, TTX-S currents in axotomized neurons reprimed four times faster than control TTX-S currents. These data indicate that axotomy of spinal neurons is followed by downregulation of TTX-R current and by the emergence of a rapidly repriming TTX-S current and suggest that this may be attributable to the upregulation of a sodium channel isoform that was unexpressed previously in these cells. These axotomy-induced changes in sodium currents are expected to alter excitability substantially and could underlie the molecular pathogenesis of some chronic pain syndromes associated with injury to the axons of spinal sensory neurons.

AB - Clinical and experimental studies have shown that spinal sensory neurons become hyperexcitable after axonal injury, and electrophysiological changes have suggested that this may be attributable to changes in sodium current expression. We have demonstrated previously that sodium channel α-III mRNA levels are elevated and sodium channel α-SNS mRNA levels are reduced in rat spinal sensory neurons after axotomy. In this study we show that small (C- type) rat spinal sensory neurons express sodium currents with dramatically different kinetics after axotomy produced by sciatic nerve ligation. Uninjured C-type neurons express both slowly inactivating tetrodotoxin- resistant (TTX-R) sodium current and a fast-inactivating tetrodotoxin- sensitive (TTx-S) current that reprimes (recovers from inactivation) slowly. After axotomy, the TTX-R current density was greatly reduced. No difference was observed in the density of TTX-S currents after axotomy, and their voltage dependence was not different from controls. However, TTX-S currents in axotomized neurons reprimed four times faster than control TTX-S currents. These data indicate that axotomy of spinal neurons is followed by downregulation of TTX-R current and by the emergence of a rapidly repriming TTX-S current and suggest that this may be attributable to the upregulation of a sodium channel isoform that was unexpressed previously in these cells. These axotomy-induced changes in sodium currents are expected to alter excitability substantially and could underlie the molecular pathogenesis of some chronic pain syndromes associated with injury to the axons of spinal sensory neurons.

KW - axotomy

KW - chronic pain

KW - dorsal root ganglion

KW - excitability

KW - sodium channel

KW - sodium current

UR - http://www.scopus.com/inward/record.url?scp=0030997916&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030997916&partnerID=8YFLogxK

M3 - Article

C2 - 9133375

AN - SCOPUS:0030997916

VL - 17

SP - 3503

EP - 3514

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 10

ER -