The role of glial-specific Kir4.1 in normal and pathological states of the CNS.
The role of glial-specific Kir4.1 in normal and pathological states of the CNS.
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DOI：
10.1007/s00401-016-1553-1
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发表时间：
2016-07
影响因子：
12.7
通讯作者：
Olsen ML
中科院分区：
文献类型：
--
作者：
Nwaobi SE;Cuddapah VA;Patterson KC;Randolph AC;Olsen ML
Kir4.1是一种内向整流性钾离子通道，仅在中枢神经系统的胶质细胞中表达。在神经胶质中，Kir4.1参与多种功能，包括细胞外K+稳态，维持星形胶质细胞静息膜电位，细胞体积调节和促进谷氨酸摄取。在啮齿动物模型中Kir4.1的敲除导致严重的神经缺陷，包括共济失调、癫痫发作、感觉神经性耳聋和出生后早期死亡。越来越多的证据表明Kir4.1在中枢神经系统中起着不可或缺的作用，促使许多实验室研究Kir4.1在人类疾病中的潜在作用。在这篇文章中，我们回顾了越来越多的证据表明Kir4.1在广泛的神经系统疾病。最近的文献表明Kir4.1功能障碍促进神经元过度兴奋，并可能导致癫痫。基因筛选表明，编码Kir4.1的基因KCNJ 10的突变导致Seepsin/EAST综合征，其特征在于早发性癫痫发作，言语和运动技能受损，严重的认知缺陷和盐浪费。KCNJ 10还与包括自闭症在内的发育障碍有关。脑外伤、缺血和炎症都与星形胶质细胞Kir4.1电流振幅降低和星形胶质细胞功能障碍有关。此外，神经退行性疾病如阿尔茨海默病和肌萎缩性侧索硬化症表现出Kir4.1的缺失。这在亨廷顿氏病的背景下特别令人兴奋，亨廷顿氏病是另一种神经退行性疾病，其中Kir4.1的恢复改善了运动缺陷，降低了中等多刺神经元的过度兴奋性，并延长了小鼠模型的存活。了解Kir4.1的表达和调节对于确定该通道是否可以用于治疗益处至关重要。
Kir4.1 is an inwardly rectifying K+ channel expressed exclusively in glial cells in the central nervous system. In glia, Kir4.1 is implicated in several functions which include extracellular K+ homeostasis, maintenance of astrocyte resting membrane potential, cell volume regulation and facilitation of glutamate uptake. Knockout of Kir4.1 in rodent models leads to severe neurological deficits, including ataxia, seizures, sensorineural deafness, and early postnatal death. Accumulating evidence indicates that Kir4.1 plays an integral role in the central nervous system, prompting many laboratories to study the potential role that Kir4.1 plays in human disease. In this article, we review the growing evidence implicating Kir4.1 in a wide array of neurological disease. Recent literature suggests Kir4.1 dysfunction facilitates neuronal hyperexcitability and may contribute to epilepsy. Genetic screens demonstrate that mutations of KCNJ10, the gene encoding Kir4.1, causes SeSAME/EAST syndrome, which is characterized by early onset seizures, compromised verbal and motor skills, profound cognitive deficits, and salt wasting. KCNJ10 has also been linked to developmental disorders including autism. Cerebral trauma, ischemia, and inflammation are all associated with decreased astrocytic Kir4.1 current amplitude and astrocytic dysfunction. Additionally, neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis demonstrate loss of Kir4.1. This is particularly exciting in the context of Huntington’s disease, another neurodegenerative disease in which restoration of Kir4.1 ameliorated motor deficits, decreased medium spiny neuron hyperexcitability, and extended survival in mouse models. Understanding the expression and regulation of Kir4.1 will be critical in determining if this channel can be exploited for therapeutic benefit.
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影响因子：
5.3
作者：
Djukic, Biljana;Casper, Kristen B.;McCarthy, Ken D.
通讯作者：
McCarthy, Ken D.
DOI：
10.1126/science.1190721
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gourine AV;Kasymov V;Marina N;Tang F;Figueiredo MF;Lane S;Teschemacher AG;Spyer KM;Deisseroth K;Kasparov S
通讯作者：
Kasparov S
影响因子：
2.5
作者：
D'Ambrosio, R;Gordon, DS;Winn, HR
通讯作者：
Winn, HR
DOI：
10.1016/0165-3806(89)90288-5
发表时间：
1989-04-01
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
HABLITZ, JJ;HEINEMANN, U
通讯作者：
HEINEMANN, U
影响因子：
2.5
作者：
Bordey, A;Sontheimer, H
通讯作者：
Sontheimer, H