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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Voltage-gated potassium channel KCNV2 (Kv8.2) contributes to epilepsy susceptibility
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Voltage-gated potassium channel KCNV2 (Kv8.2) contributes to epilepsy susceptibility

机译：电压门控钾通道KCNV2（Kv8.2）有助于癫痫易感性

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摘要

Mutations in voltage-gated ion channels are responsible for several types of epilepsy. Genetic epilepsies often exhibit variable severity in individuals with the same mutation, which may be due to variation in genetic modifiers. The Scn2a~(Q54) transgenic mouse model has a sodium channel mutation and exhibits epilepsy with strain-dependent severity. We previously mapped modifier loci that influence Scn2a(Q54) phenotype severity and identified Kcnv2, encoding the voltage-gated potassium channel subunit Kv8.2, as a candidate modifier. In this study, we demonstrate a threefold increase in hippocampal Kcnv2 expression associated with more severe epilepsy. In vivo exacerbation of the phenotype by Kcnv2 transgenes supports its identification as an epilepsy modifier. The contribution of KCNV2 to human epilepsy susceptibility is supported by identification of two nonsynonymous variants in epilepsy patients that alter function of Kv2.1/Kv8.2 heterotetrameric potassium channels. Our results demonstrate that altered potassium subunit function influences epilepsy susceptibility and implicate Kcnv2 as an epilepsy gene.
机译：电压门控离子通道中的突变可导致多种类型的癫痫。遗传性癫痫通常在具有相同突变的个体中表现出不同的严重程度，这可能是由于遗传修饰因子的差异所致。 Scn2a〜（Q54）转基因小鼠模型具有钠通道突变，并表现出癫痫病的严重程度。我们先前映射影响Scn2a（Q54）表型严重性的修饰位点，并确定了编码电压门控钾通道亚基Kv8.2的Kcnv2作为候选修饰物。在这项研究中，我们证明与更严重的癫痫相关的海马Kcnv2表达增加了三倍。 Kcnv2转基因在体内表型的加剧支持其鉴定为癫痫调节剂。通过在癫痫患者中鉴定两个改变Kv2.1 / Kv8.2异四聚体钾通道功能的非同义变体，可以支持KCNV2对人类癫痫易感性的贡献。我们的结果表明，改变的钾亚基功能影响癫痫易感性，并暗示Kcnv2作为癫痫基因。

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