Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/43968
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Type: Journal article
Title: A childhood epilepsy mutation reveals a role for developmentally regulated splicing of a sodium channel
Author: Xu, R.
Thomas, E.
Jenkins, M.
Gazina, E.
Chiu, C.
Heron, S.
Mulley, J.
Scheffer, I.
Berkovic, S.
Petrou, S.
Citation: Molecular and Cellular Neuroscience, 2007; 35(2):292-301
Publisher: Academic Press Inc Elsevier Science
Issue Date: 2007
ISSN: 1044-7431
1095-9327
Statement of
Responsibility: 
Ruwei 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
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.
Keywords: Cell Line, Transformed; Humans; Epilepsy; Sodium Channels; Nerve Tissue Proteins; DNA Mutational Analysis; Electric Stimulation; Dose-Response Relationship, Radiation; RNA Splicing; Membrane Potentials; Mutation; Models, Biological; Computer Simulation; Adult; Infant; NAV1.2 Voltage-Gated Sodium Channel
Description: Copyright © 2007 Elsevier Inc. All rights reserved.
RMID: 0020070912
DOI: 10.1016/j.mcn.2007.03.003
Description (link): http://www.elsevier.com/wps/find/journaldescription.cws_home/622917/description#description
Appears in Collections:Molecular and Biomedical Science publications

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