A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons

Anthony M. Rush, Sulayman D. Dib-Hajj, Shujun Liu, Theodore Cummins, Joel A. Black, Stephen G. Waxman

Research output: Contribution to journalArticle

282 Citations (Scopus)

Abstract

Disease-producing mutations of ion channels are usually characterized as producing hyperexcitability or hypoexcitability. We show here that a single mutation can produce hyperexcitability in one neuronal cell type and hypoexcitability in another neuronal cell type. We studied the functional effects of a mutation of sodium channel Nav1.7 associated with a neuropathic pain syndrome, erythermalgia, within sensory and sympathetic ganglion neurons, two cell types where Nav1.7 is normally expressed. Although this mutation depolarizes resting membrane potential in both types of neurons, it renders sensory neurons hyperexcitable and sympathetic neurons hypoexcitable. The selective presence, in sensory but not sympathetic neurons, of the Nav1.8 channel, which remains available for activation at depolarized membrane potentials, is a major determinant of these opposing effects. These results provide a molecular basis for the sympathetic dysfunction that has been observed in erythermalgia. Moreover, these findings show that a single ion channel mutation can produce opposing phenotypes (hyperexcitability or hypoexcitability) in the different cell types in which the channel is expressed.

Original languageEnglish
Pages (from-to)8245-8250
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number21
DOIs
StatePublished - May 23 2006

Fingerprint

Sodium Channels
Neurons
Mutation
Erythromelalgia
Ion Channels
Membrane Potentials
Sensory Ganglia
Sympathetic Ganglia
Neuralgia
Sensory Receptor Cells
Phenotype

Keywords

  • Inherited erythermalgia
  • Neuropathic pain
  • Primary erythromelalgia
  • Sodium channelopathy

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. / Rush, Anthony M.; Dib-Hajj, Sulayman D.; Liu, Shujun; Cummins, Theodore; Black, Joel A.; Waxman, Stephen G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 21, 23.05.2006, p. 8245-8250.

Research output: Contribution to journalArticle

Rush, Anthony M. ; Dib-Hajj, Sulayman D. ; Liu, Shujun ; Cummins, Theodore ; Black, Joel A. ; Waxman, Stephen G. / A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 21. pp. 8245-8250.
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