The role of an inwardly rectifying K(+) channel (Kir4.1) in the inner ear and hearing loss.
The role of an inwardly rectifying K(+) channel (Kir4.1) in the inner ear and hearing loss.
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DOI：
10.1016/j.neuroscience.2014.01.036
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发表时间：
2014-04-18
期刊：
影响因子：
3.3
通讯作者：
Zhao HB
中科院分区：
文献类型：
--
作者：
Chen J;Zhao HB
KCNJ10基因编码内向整流钾通道Kir4.1亚基，在内耳和听力中起重要作用。KCNJ10的突变或缺陷可导致EAST或SEST综合征的听力损失。本文就Kir4.1钾通道在内耳和听觉中的表达和功能作一综述。我们首先介绍Kir钾通道的一般信息。本文综述了Kir4.1通道在内耳的表达和功能，特别是在耳蜗内电位（EP）产生中的作用。最后，我们综述了KCNJ10突变导致的听力损失和功能障碍。Kir4.1在血管纹的中间细胞和耳蜗神经节的卫星细胞的顶膜上强烈表达。Kir4.1在耳蜗发育和听力中起着重要的作用，它通过细胞外K+稳态的两个不同方面：第一，它参与EP的产生和维持以及中阶内淋巴中高K+浓度。第二，Kir4.1是螺旋神经节神经元周围的卫星胶质细胞中的主要K+通道，用于在兴奋期间吸收神经节神经元排出的K+离子。Kir4.1缺陷导致听力损失，EP缺失和螺旋神经节神经元变性。耳聋突变体显示“功能丧失”和降低的通道膜靶向和电流，这可以通过与野生型Kir4.1共表达来挽救。本文综述了Kir钾通道在内耳的功能及其在KCNJ10缺乏性耳聋发病机制中的作用，并为针对KCNJ10缺乏性耳聋的治疗提供了新的思路。
The KCNJ10 gene which encodes an inwardly rectifying K+ channel Kir4.1 subunit plays an essential role in the inner ear and hearing. Mutations or deficiency of KCNJ10 can cause hearing loss with EAST or SeSAME syndromes. This review mainly focuses on the expression and function of Kir4.1 potassium channels in the inner ear and hearing. We first introduce general information about Kir potassium channels. Then, we review the expression and function of Kir4.1 channels in the inner ear, especially in endocochlear potential (EP) generation. Finally, we review KCNJ10 mutation induced hearing loss and functional impairments. Kir4.1 is strongly expressed on the apical membrane of intermediate cells in the stria vascularis and in the satellite cells of cochlear ganglia. Functionally, Kir4.1 has critical roles in cochlear development and hearing through two distinct aspects of extracellular K+ homeostasis: First, it participates in the generation and maintenance of EP and high K+ concentration in the endolymph inside the scala media. Second, Kir4.1 is the major K+ channel in satellite glial cells surrounding spiral ganglion neurons to sink K+ ions expelled by the ganglion neurons during excitation. Kir4.1 deficiency leads to hearing loss with the absence of EP and spiral ganglion neuron degeneration. Deafness mutants show “loss-of-function” and reduced channel membrane-targeting and currents, which can be rescued upon by co-expression with wild-type Kir4.1. This review provides insights for further understanding Kir potassium channel function in the inner ear and the pathogenesis of deafness due to KCNJ10 deficiency, and also provides insights for developing therapeutic strategies targeting this deafness.
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DOI：
10.1073/pnas.92.15.6753
发表时间：
1995-07-18
影响因子：
11.1
作者：
BREDT, DS;WANG, TL;SNYDER, SH
通讯作者：
SNYDER, SH
DOI：
10.1016/0165-3806(87)90140-4
发表时间：
1987-03-01
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
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通讯作者：
COLEMAN, JR
影响因子：
3.2
作者：
Crouch, JJ;Sakaguchi, N;Schulte, BA
通讯作者：
Schulte, BA
DOI：
10.1016/j.ijporl.2010.06.002
发表时间：
2010-09-01
影响因子：
1.5
作者：
Jonard, Laurence;Niasme-Grare, Magali;Marlin, Sandrine
通讯作者：
Marlin, Sandrine
影响因子：
--
作者：
Freudenthal, Bernard;Kulaveerasingam, Duvaraka;Zdebik, Anselm A.
通讯作者：
Zdebik, Anselm A.