KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness
KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness
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DOI：
10.1016/s0092-8674(00)80556-5
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发表时间：
1999-02-05
期刊：
影响因子：
64.5
通讯作者：
Jentsch, TJ
中科院分区：
文献类型：
--
作者：
Kubisch, C;Schroeder, BC;Jentsch, TJ
钾通道调节电信号和生物体液的离子组成。K+通道基因家族KCNQ分支的三个已知基因突变是遗传性心律失常（在某些情况下与耳聋有关）和新生儿癫痫的基础。我们现在已经克隆了KCNQ 4，它是该分支的一个新成员。它映射到DFNA 2基因座的一种形式的非综合征显性耳聋。在耳蜗中，它在感觉外毛细胞中表达，DFNA 2家系中该基因的突变改变了KCNQ 4孔区域中的残基。它消除了野生型KCNQ4的钾电流，它对KCNQ4产生了强烈的显性负效应。KCNQ1突变通过影响内淋巴分泌导致耳聋，而导致KCNQ4相关听力损失的机制是外毛细胞固有的。
Potassium channels regulate electrical signaling and the ionic composition of biological fluids. Mutations in the three known genes of the KCNQ branch of the K+ channel gene family underlie inherited cardiac arrhythmias (in some cases associated with deafness) and neonatal epilepsy. We have now cloned KCNQ4, a novel member of this branch. It maps to the DFNA2 locus for a form of nonsyndromic dominant deafness. In the cochlea, it is expressed in sensory outer hair cells, A mutation in this gene in a DFNA2 pedigree changes a residue in the KCNQ4 pore region. It abolishes the potassium currents of wild-type KCNQ4 on which it exerts a strong dominant-negative effect. Whereas mutations in KCNQ1 cause deafness by affecting endolymph secretion, the mechanism leading to KCNQ4-related hearing loss is intrinsic to outer hair cells.