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https://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. |
DOI: | 10.1016/j.mcn.2007.03.003 |
Description (link): | http://www.elsevier.com/wps/find/journaldescription.cws_home/622917/description#description |
Published version: | http://dx.doi.org/10.1016/j.mcn.2007.03.003 |
Appears in Collections: | Aurora harvest 6 Molecular and Biomedical Science publications |
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