Expression and localization of voltage dependent potassium channel Kv4.2 in epilepsy associated focal lesions
Expression and localization of voltage dependent potassium channel Kv4.2 in epilepsy associated focal lesions
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DOI：
10.1016/j.nbd.2009.06.016
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发表时间：
2009-10-01
影响因子：
6.1
通讯作者：
Jeromin, A.
中科院分区：
文献类型：
--
作者：
Aronica, E.;Boer, K.;Jeromin, A.
越来越多的观察表明电压门控钾通道在癫痫中起重要作用。我们研究了细胞特异性分布的Kv4.2，磷酸化（p）Kv4.2和Kv4.2相互作用蛋白NCS-1在不同的癫痫相关的局灶性病变使用免疫细胞化学。在海马硬化（HS）中，Kv4.2和pKv4.2免疫反应性（IR）在具有显著神经元细胞丢失的区域的神经元中降低。在HS和畸形的皮质发育（MCD），强烈的标记被发现在神经元胞体，但不是在树突。在所有病变类型的神经元中观察到强NCS-1 IR。Western印迹分析表明，增加总Kv4.2在所有的病变和激活的ERK通路在HS和神经节细胞胶质瘤。这些研究结果表明，Kv4.2在神经元和神经胶质细胞中表达，其调节可能涉及钾通道相互作用蛋白，通道的亚细胞定位的改变，以及磷酸化介导的翻译后修饰。(C)2009 Elsevier Inc. All rights reserved.
An increasing number of observations suggest an important role for voltage-gated potassium (Kv) channels in epilepsy. We studied the cell-specific distribution of Kv4.2, phosphorylated (p) Kv4.2 and the Kv4.2 interacting protein NCS-1 using immunocytochemistry in different epilepsy-associated focal lesions. In hippocampal sclerosis (HS), Kv4.2 and pKv4.2 immunoreactivity (IR) was reduced in the neuropil in regions with prominent neuronal cell loss. In both HS and malformations of cortical development (MCD), intense labeling was found in neuronal somata, but not in dendrites. Strong NCS-1 IR was observed in neurons in all lesion types. Western blot analysis demonstrated an increase of total Kv4.2 in all lesions and activation of the ERK pathway in HS and ganglioglioma. These findings indicate that Kv4.2 is expressed in both neuronal and glial cells and its regulation may involve potassium channel interacting proteins, alterations in the subcellular localization of the channel, as well as phosphorylation-mediated posttranslational modifications. (C) 2009 Elsevier Inc. All rights reserved.