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 Scopus citations

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

ASJC Scopus subject areas

  • Medicine(all)

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    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).