Diverse functions and dynamic expression of neuronal sodium channels

Stephen G. Waxman, Theodore Cummins, Joel A. Black, Sulayman Dib-Hajj

Research output: Chapter in Book/Report/Conference proceedingChapter

31 Citations (Scopus)

Abstract

Nearly a dozen genes encode different Na+ channels, sharing a common overall motif but with subtly different amino acid sequences. Physiological signatures have now been established for some Na+ channels and it is clear that from a functional point of view, Na+ channels are not all the same: different channels can have different physiological characteristics, and they can play different roles in the physiology of excitable cells. Moreover, the expression of Na+ channels within neurons is not a static process. Plasticity of Na+ channel gene expression occurs in the normal nervous system, where it accompanies transitions between different physiological states (e.g. low-frequency versus high-frequency firing states) in some types of neurons. Maladaptive changes in Na+ channel gene expression also occur in some pathological neurons. For example, transaction of the peripheral axons of spinal sensory neurons triggers down-regulation of some Na+ channel genes and up-regulation of others, resulting in changes nNa+ current expression that produce hyperexcitability, thereby contributing to chronic pain. There is also recent evidence for the expression of normally silent Na+ channel genes in Purkinje cells in experimental models of demyelinatmg diseases and in a human disease, multiple sclerosis; this dysregulation of Na+ channel expression may intefere with neuronal function in these disorders. The diversity and dynamic nature of Na+ channel expression introduce a high degree of complexity into the nervous system and present challenges for neuroscientists. In addition, they may present therapeutic opportunities as selective modulators for various Na+ channel subtypes become available.

Original languageEnglish
Title of host publicationNovartis Foundation Symposium
Pages34-60
Number of pages27
Volume241
StatePublished - 2002
Externally publishedYes

Publication series

NameNovartis Foundation Symposium
Volume241

Fingerprint

Sodium Channels
Neurons
Nervous System
Genes
Gene Expression
Cell Physiological Phenomena
Purkinje Cells
Sensory Receptor Cells
Chronic Pain
Multiple Sclerosis
Axons
Amino Acid Sequence
Theoretical Models
Up-Regulation
Down-Regulation
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Waxman, S. G., Cummins, T., Black, J. A., & Dib-Hajj, S. (2002). Diverse functions and dynamic expression of neuronal sodium channels. In Novartis Foundation Symposium (Vol. 241, pp. 34-60). (Novartis Foundation Symposium; Vol. 241).

Diverse functions and dynamic expression of neuronal sodium channels. / Waxman, Stephen G.; Cummins, Theodore; Black, Joel A.; Dib-Hajj, Sulayman.

Novartis Foundation Symposium. Vol. 241 2002. p. 34-60 (Novartis Foundation Symposium; Vol. 241).

Research output: Chapter in Book/Report/Conference proceedingChapter

Waxman, SG, Cummins, T, Black, JA & Dib-Hajj, S 2002, Diverse functions and dynamic expression of neuronal sodium channels. in Novartis Foundation Symposium. vol. 241, Novartis Foundation Symposium, vol. 241, pp. 34-60.
Waxman SG, Cummins T, Black JA, Dib-Hajj S. Diverse functions and dynamic expression of neuronal sodium channels. In Novartis Foundation Symposium. Vol. 241. 2002. p. 34-60. (Novartis Foundation Symposium).
Waxman, Stephen G. ; Cummins, Theodore ; Black, Joel A. ; Dib-Hajj, Sulayman. / Diverse functions and dynamic expression of neuronal sodium channels. Novartis Foundation Symposium. Vol. 241 2002. pp. 34-60 (Novartis Foundation Symposium).
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