Familial epilepsies are often caused by mutations of voltage-gated Na <sup>+</sup> 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 Na<sub>v</sub>1.1 (SCN1A) Na<sup>+</sup> 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 <30°C, showing that the mutant is trafficking defective, thus far the first case among neuronal Na<sup>+</sup> 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. Copyright © 2007 Society for Neuroscience.
Rusconi, R., Scalmani, P., Restano Cassulini, R., Giunti, G., Gambardella, A., Franceschetti, S., et al. (2007). Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 (SCN1A) Na+ channel mutant. THE JOURNAL OF NEUROSCIENCE, 27(41), 11037-11046 [10.1523/JNEUROSCI.3515-07.2007].
Citazione: | Rusconi, R., Scalmani, P., Restano Cassulini, R., Giunti, G., Gambardella, A., Franceschetti, S., et al. (2007). Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 (SCN1A) Na+ channel mutant. THE JOURNAL OF NEUROSCIENCE, 27(41), 11037-11046 [10.1523/JNEUROSCI.3515-07.2007]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Titolo: | Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 (SCN1A) Na+ channel mutant | |
Autori: | Rusconi, R; Scalmani, P; Restano Cassulini, R; Giunti, G; Gambardella, A; Franceschetti, S; Annesi, G; Wanke, E; Mantegazza, M | |
Autori: | ||
Data di pubblicazione: | 2007 | |
Lingua: | English | |
Rivista: | THE JOURNAL OF NEUROSCIENCE | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1523/JNEUROSCI.3515-07.2007 | |
Appare nelle tipologie: | 01 - Articolo su rivista |