K(+) channelepsy: progress in the neurobiology of potassium channels and epilepsy.
K(+) channelepsy: progress in the neurobiology of potassium channels and epilepsy.
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DOI：
10.3389/fncel.2013.00134
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发表时间：
2013-09-13
影响因子：
5.3
通讯作者：
Pessia M
中科院分区：
文献类型：
--
作者：
D'Adamo MC;Catacuzzeno L;Di Giovanni G;Franciolini F;Pessia M
K+通道是癫痫敏感性的重要决定因素。这些膜蛋白由70多个基因编码，构成了最大的一组离子通道，可以微调大脑中神经元和非神经元细胞的电活动。它们的普遍性和极高的遗传和功能多样性是任何其他离子通道类型所无法比拟的，即使在没有初级通道缺陷的情况下，K+通道也是遗传变异或K+依赖的动态平衡扰动的主要靶点。因此，许多遗传性或获得性K+通道功能障碍与包括癫痫在内的几种神经综合征相关也就不足为奇了，这往往会导致相关疾病的分类混乱。因此，我们建议将不同癫痫的K+通道缺陷命名为“K+通道缺失”，并在广泛使用的K+通道分类之后引入一个新的命名法(例如，Kx.y-通道缺失)，该分类也可以用于容易地识别涉及Na+(例如，Navx.y-表型)、Ca+(例如，Cavx.y-表型)和Cl-−通道的其他通道病变。此外，我们讨论了K+通道和相关蛋白的新的遗传缺陷，这些缺陷是人类不同癫痫表型的基础，并批判性地分析了这种疾病的神经生物学方面的最新进展，这也是通过对有价值的癫痫动物模型的研究提供的。这里讨论的丰富而多样的证据有力地促进了对特发性癫痫患者K+通道和相关蛋白编码基因变异的评估，为未来的研究提供了新的途径，并强调这些蛋白是关键的药理靶点。
K+ channels are important determinants of seizure susceptibility. These membrane proteins, encoded by more than 70 genes, make the largest group of ion channels that fine-tune the electrical activity of neuronal and non-neuronal cells in the brain. Their ubiquity and extremely high genetic and functional diversity, unmatched by any other ion channel type, place K+ channels as primary targets of genetic variations or perturbations in K+-dependent homeostasis, even in the absence of a primary channel defect. It is therefore not surprising that numerous inherited or acquired K+ channels dysfunctions have been associated with several neurologic syndromes, including epilepsy, which often generate confusion in the classification of the associated diseases. Therefore, we propose to name the K+ channels defects underlying distinct epilepsies as “K+ channelepsies,” and introduce a new nomenclature (e.g., Kx.y-channelepsy), following the widely used K+ channel classification, which could be also adopted to easily identify other channelopathies involving Na+ (e.g., Navx.y-phenotype), Ca2+ (e.g., Cavx.y-phenotype), and Cl− channels. Furthermore, we discuss novel genetic defects in K+ channels and associated proteins that underlie distinct epileptic phenotypes in humans, and analyze critically the recent progress in the neurobiology of this disease that has also been provided by investigations on valuable animal models of epilepsy. The abundant and varied lines of evidence discussed here strongly foster assessments for variations in genes encoding for K+ channels and associated proteins in patients with idiopathic epilepsy, provide new avenues for future investigations, and highlight these proteins as critical pharmacological targets.
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