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

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dc.contributor.authorXu, R.
dc.contributor.authorThomas, E.
dc.contributor.authorJenkins, M.
dc.contributor.authorGazina, E.
dc.contributor.authorChiu, C.
dc.contributor.authorHeron, S.
dc.contributor.authorMulley, J.
dc.contributor.authorScheffer, I.
dc.contributor.authorBerkovic, S.
dc.contributor.authorPetrou, S.
dc.date.issued2007
dc.descriptionCopyright © 2007 Elsevier Inc. All rights reserved.
dc.description.abstractSeizure 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.
dc.description.statementofresponsibilityRuwei Xu, Evan A. Thomas, Misty Jenkins, Elena V. Gazina, Cindy Chiu, Sarah E. Heron, John C. Mulley, Ingrid E. Scheffer, Samuel F. Berkovic and Steven Petrou
dc.description.urihttp://www.elsevier.com/wps/find/journaldescription.cws_home/622917/description#description
dc.identifier.citationMolecular and Cellular Neuroscience, 2007; 35(2):292-301
dc.identifier.doi10.1016/j.mcn.2007.03.003
dc.identifier.issn1044-7431
dc.identifier.issn1095-9327
dc.identifier.orcidHeron, S. [0000-0001-8759-6748]
dc.identifier.urihttp://hdl.handle.net/2440/43968
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.source.urihttps://doi.org/10.1016/j.mcn.2007.03.003
dc.subjectCell Line, Transformed
dc.subjectHumans
dc.subjectEpilepsy
dc.subjectSodium Channels
dc.subjectNerve Tissue Proteins
dc.subjectDNA Mutational Analysis
dc.subjectElectric Stimulation
dc.subjectDose-Response Relationship, Radiation
dc.subjectRNA Splicing
dc.subjectMembrane Potentials
dc.subjectMutation
dc.subjectModels, Biological
dc.subjectComputer Simulation
dc.subjectAdult
dc.subjectInfant
dc.subjectNAV1.2 Voltage-Gated Sodium Channel
dc.titleA childhood epilepsy mutation reveals a role for developmentally regulated splicing of a sodium channel
dc.typeJournal article
pubs.publication-statusPublished

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