Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy

Theodore Cummins, Sulayman D. Dib-Hajj, Stephen G. Waxman

Research output: Contribution to journalArticle

267 Citations (Scopus)

Abstract

Although the physiological basis of erythermalgia, an autosomal dominant painful neuropathy characterized by redness of the skin and intermittent burning sensation of extremities, is not known, two mutations of Nav1.7, a sodium channel that produces a tetrodotoxin-sensitive, fast-inactivating current that is preferentially expressed in dorsal root ganglia (DRG) and sympathetic ganglia neurons, have recently been identified in patients with primary erythermalgia. Nav1.7 is preferentially expressed in small-diameter DRG neurons, most of which are nociceptors, and is characterized by slow recovery from inactivation and by slow closed-state inactivation that results in relatively large responses to small, subthreshold depolarizations. Here we show that these mutations in Nav1.7 produce a hyperpolarizing shift in activation and slow deactivation. We also show that these mutations cause an increase in amplitude of the current produced by Nav1.7 in response to slow, small depolarizations. These observations provide the first demonstration of altered sodium channel function associated with an inherited painful neuropathy and suggest that these physiological changes, which confer hyperexcitability on peripheral sensory and sympathetic neurons, contribute to symptom production in hereditary erythermalgia.

Original languageEnglish
Pages (from-to)8232-8236
Number of pages5
JournalJournal of Neuroscience
Volume24
Issue number38
DOIs
StatePublished - Sep 22 2004

Fingerprint

Erythromelalgia
Sodium Channels
Spinal Ganglia
Mutation
Neurons
Nociceptors
Sympathetic Ganglia
Tetrodotoxin
Sensory Receptor Cells
Extremities
Skin
Painful Neuropathy

Keywords

  • Dorsal root ganglion
  • Hyperpolarization
  • Neuropathic pain
  • Skeletal sodium channel
  • Tetrodotoxin sensitive
  • Voltage clamp

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. / Cummins, Theodore; Dib-Hajj, Sulayman D.; Waxman, Stephen G.

In: Journal of Neuroscience, Vol. 24, No. 38, 22.09.2004, p. 8232-8236.

Research output: Contribution to journalArticle

Cummins, Theodore ; Dib-Hajj, Sulayman D. ; Waxman, Stephen G. / Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 38. pp. 8232-8236.
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