Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 Na+ channel mutant

Raffaella Rusconi, Paolo Scalmani, Rita Restano Cassulini, Giulia Giunti, Antonio Gambardella, Silvana Franceschetti, Grazia Annesi, Enzo Wanke, Massimo Mantegazza

Research output: Contribution to journalArticle

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Abstract

Familial epilepsies are often caused by mutations of voltage-gated Na + channels, but correlation genotype-phenotype is not yet clear. In particular, the cause of phenotypic variability observed in some epileptic families is unclear. We studied Nav1.1 (SCN1A) Na+ channel α subunit M1841T mutation, identified in a family characterized by a particularly large phenotypic spectrum. The mutant is a loss of function becausewhenexpressed alone, the current was no greater than background. Function was restored by incubation at temperature + channels. Importantly, also molecular interactions with modulatory proteins or drugs were able to rescue the mutant. Protein-protein interactions may modulate the effect of the mutation in vivo and thus phenotype; variability in their strength may be one of the causes of phenotypic variability in familial epilepsy. Interacting drugs may be used to rescue the mutant in vivo.

Original languageEnglish
Pages (from-to)11037-11046
Number of pages10
JournalJournal of Neuroscience
Volume27
Issue number41
DOIs
Publication statusPublished - Oct 10 2007

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Mutation
Epilepsy
Proteins
Genetic Association Studies
Pharmaceutical Preparations
Phenotype
Temperature

Keywords

  • Current
  • Epilepsy
  • Excitability
  • GEFS+
  • SCN1A
  • Seizure
  • SMEI
  • Sodium
  • Trafficking

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Rusconi, R., Scalmani, P., Cassulini, R. R., Giunti, G., Gambardella, A., Franceschetti, S., ... Mantegazza, M. (2007). Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 Na+ channel mutant. Journal of Neuroscience, 27(41), 11037-11046. https://doi.org/10.1523/JNEUROSCI.3515-07.2007

Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 Na+ channel mutant. / Rusconi, Raffaella; Scalmani, Paolo; Cassulini, Rita Restano; Giunti, Giulia; Gambardella, Antonio; Franceschetti, Silvana; Annesi, Grazia; Wanke, Enzo; Mantegazza, Massimo.

In: Journal of Neuroscience, Vol. 27, No. 41, 10.10.2007, p. 11037-11046.

Research output: Contribution to journalArticle

Rusconi, R, Scalmani, P, Cassulini, RR, Giunti, G, Gambardella, A, Franceschetti, S, Annesi, G, Wanke, E & Mantegazza, M 2007, 'Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 Na+ channel mutant', Journal of Neuroscience, vol. 27, no. 41, pp. 11037-11046. https://doi.org/10.1523/JNEUROSCI.3515-07.2007
Rusconi, Raffaella ; Scalmani, Paolo ; Cassulini, Rita Restano ; Giunti, Giulia ; Gambardella, Antonio ; Franceschetti, Silvana ; Annesi, Grazia ; Wanke, Enzo ; Mantegazza, Massimo. / Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 Na+ channel mutant. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 41. pp. 11037-11046.
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