A childhood epilepsy mutation reveals a role for developmentally regulated splicing of a sodium channel.
Mol Cell Neurosci
; 35(2): 292-301, 2007 Jun.
Article
em En
| MEDLINE
| ID: mdl-17467289
ABSTRACT
Seizure susceptibility is high in human infants compared to adults, presumably because of developmentally regulated changes in neural excitability. Benign familial neonatal-infantile seizures (BFNIS), characterized by both early onset and remission, are caused by mutations in the gene encoding a human sodium channel (NaV1.2). We analyzed neonatal and adult splice forms of NaV1.2 with a BFNIS mutation (L1563V) in human embryonic kidney cells. Computer modeling revealed that neonatal channels are less excitable than adult channels. Introduction of the mutation increased excitability in the neonatal channels to a level similar to adult channels. By contrast, the mutation did not affect the adult channel variant. This "adult-like" increased excitability is likely to be the mechanism underlying BFNIS in infants with this mutation. More generally, developmentally regulated NaV1.2 splicing may be one mechanism that counters the normally high excitability of neonatal neurons and helps to reduce seizure susceptibility in normal human infants.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Sódio
/
Splicing de RNA
/
Epilepsia
/
Potenciais da Membrana
/
Proteínas do Tecido Nervoso
Limite:
Adult
/
Humans
/
Infant
Idioma:
En
Revista:
Mol Cell Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Austrália