Nav 1.1 channels with mutations of severe myoclonic epilepsy in infancy display attenuated currents
Nav 1.1 channels with mutations of severe myoclonic epilepsy in infancy display attenuated currents
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DOI：
10.1016/s0920-1211(03)00084-6
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发表时间：
2003-05-01
影响因子：
2.2
通讯作者：
Yamakawa, K
中科院分区：
文献类型：
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作者：
Sugawara, T;Tsurubuchi, Y;Yamakawa, K
婴儿期严重肌阵挛性癫痫 (SMEI) 的特点是顽固性热性和非热性惊厥、严重智力衰退，并在出生后第一年发病。在 SMEI 患者中已发现编码电压门控 Na+ 通道 α 亚基 I 型 (Na-v 1. 1) 的 SCN1A 基因的无义、移码和错义突变。在这里，我们对表达带有 SMEI 无义和错义突变的人 Na-v 1. 1 通道的 HEK293 细胞进行全细胞膜片钳分析。突变通道显示出明显减弱或几乎检测不到的内向钠电流。我们的研究结果表明 SMEI 突变会导致功能丧失，并可能促进 SMEI 表型的发展。 (C) 2003 Elsevier Science B.V. 保留所有权利。
Severe myoclonic epilepsy in infancy (SMEI) is characterized by intractable febrile and afebrile seizures, severe mental decline, and onset during the first year of life. Nonsense, frameshift, and missense mutations of SCN1A gene encoding the voltage-gated Na+ channel alpha-subunit type I (Na-v 1. 1) have been identified in patients with SMEI. Here, we performed whole-cell patch-clamp analyses on HEK293 cells expressing human Na-v 1. 1 channels bearing SMEI nonsense and missense mutations. The mutant channels showed remarkably attenuated or barely detectable inward sodium currents. Our findings indicate that SMEI mutations lead to loss-of-function and may contribute to the development of SMEI phenotypes. (C) 2003 Elsevier Science B.V. All rights reserved.