Mutations of voltage-gated sodium channels in movement disorders and epilepsy

Miriam H. Meisler*, Jennifer A. Kearney, Leslie K. Sprunger, Bryan T. MacDonald, David A. Buchner, Andrew Escayg

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Spontaneous and induced mutations of neuronal Na+ channels in human patients and mutant mice result in a broad range of neurological disease. Epilepsy, a disorder of neuronal hyperexcitability, has been associated with delayed inactivation of SCN2A in mice, and with altered kinetics of SCN1A in human patients. Movement disorders including tremor, ataxia, dystonia and paralysis have been observed in mice with mutations of SCN8A. Electrophysiological recordings from neurons isolated from mice with mutations in individual channels reveal the contributions of each channel to in vivo firing patterns. In addition to monogenic disease, Na+ channel mutations are likely to contribute to polygenic disease susceptibility and to normal variation in neuronal function. Advances in molecular methods coupled with genomic sequences from the Human Genome Project will permit identification of many new patient mutations and generation of animal models to dissect their physiological and cellular consequences.

Original languageEnglish (US)
Pages (from-to)72-86
Number of pages15
JournalNovartis Foundation Symposium
Volume241
StatePublished - Dec 1 2002

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Voltage-Gated Sodium Channels
Movement Disorders
Epilepsy
Mutation
Human Genome Project
Dystonia
Disease Susceptibility
Tremor
Ataxia
Paralysis
Animal Models
Neurons

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Meisler, M. H., Kearney, J. A., Sprunger, L. K., MacDonald, B. T., Buchner, D. A., & Escayg, A. (2002). Mutations of voltage-gated sodium channels in movement disorders and epilepsy. Novartis Foundation Symposium, 241, 72-86.
Meisler, Miriam H. ; Kearney, Jennifer A. ; Sprunger, Leslie K. ; MacDonald, Bryan T. ; Buchner, David A. ; Escayg, Andrew. / Mutations of voltage-gated sodium channels in movement disorders and epilepsy. In: Novartis Foundation Symposium. 2002 ; Vol. 241. pp. 72-86.
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Meisler, MH, Kearney, JA, Sprunger, LK, MacDonald, BT, Buchner, DA & Escayg, A 2002, 'Mutations of voltage-gated sodium channels in movement disorders and epilepsy', Novartis Foundation Symposium, vol. 241, pp. 72-86.

Mutations of voltage-gated sodium channels in movement disorders and epilepsy. / Meisler, Miriam H.; Kearney, Jennifer A.; Sprunger, Leslie K.; MacDonald, Bryan T.; Buchner, David A.; Escayg, Andrew.

In: Novartis Foundation Symposium, Vol. 241, 01.12.2002, p. 72-86.

Research output: Contribution to journalArticle

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Meisler MH, Kearney JA, Sprunger LK, MacDonald BT, Buchner DA, Escayg A. Mutations of voltage-gated sodium channels in movement disorders and epilepsy. Novartis Foundation Symposium. 2002 Dec 1;241:72-86.