Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 35, Issue 2, Pages 292-301Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2007.03.003
Keywords
epilepsy; sodium channels; BFNIS; developmentally regulated splicing
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Seizure susceptibility is high in human infants compared to adults, presumably because of developmentally regulated changes in neural excitability. Benign familial neonatal-infan the seizures (BFNIS), characterized by both early onset and remission, are caused by mutations in the gene encoding a human sodium channel (Na(v)1.2). We analyzed neonatal and adult splice forms of Na(v)1.2 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 Na(v)1.2 splicing may be one mechanism that counters the normally high excitability of neonatal neurons and helps to reduce seizure susceptibility in normal human infants. (c) 2007 Elsevier Inc. All rights reserved.
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