PubMed 17467289

Referenced in Channelpedia wiki pages of: Nav1.2

Automatically associated channels: Nav1.2

Title: A childhood epilepsy mutation reveals a role for developmentally regulated splicing of a sodium channel.

Authors: Ruwei Xu, Evan A Thomas, Misty Jenkins, Elena V Gazina, Cindy Chiu, Sarah E Heron, John C Mulley, Ingrid E Scheffer, Samuel F Berkovic, Steven Petrou

Journal, date & volume: Mol. Cell. Neurosci., 2007 Jun , 35, 292-301

PubMed link:

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.