期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 30, 页码 11147-11152出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0402482101
关键词
seizure; generalized epilepsy with febrile seizures plus SCN1A; electrophysiology
资金
- NIDDK NIH HHS [K01 DK061359, DK061359] Funding Source: Medline
- NINDS NIH HHS [NS32387, R01 NS032387, R37 NS032387] Funding Source: Medline
Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel alpha(1) subunit (Na(v)1.1), are associated with at least two forms of epilepsy, generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy of infancy (SMEI). We examined the functional properties of five SMEI mutations by using whole-cell patch-clamp analysis of heterologously expressed recombinant human SCN1A. Two mutations (F902C and G1674R) rendered SCN1A channels nonfunctional, and a third allele (G1749E) exhibited minimal functional alterations. However, two mutations within or near the S4 segment of the fourth repeat domain (R1648C and F1661S) conferred significant impairments in fast inactivation, including persistent, noninactivating channel activity resembling the pattern of channel dysfunction observed for alleles associated with generalized epilepsy with febrile seizures plus. Our data provide evidence for a range of SCN1A functional abnormalities in SMEI, including gain-of-function defects that were not anticipated in this disorder. Our results further indicate that a complex relationship exists between phenotype and aberrant sodium channel function in these inherited epilepsies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据