KCNQ4 K+ channels tune mechanoreceptors for normal touch sensation in mouse and man
KCNQ4 K+ channels tune mechanoreceptors for normal touch sensation in mouse and man
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DOI：
10.1038/nn.2985
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发表时间：
2012-01-01
影响因子：
25
通讯作者：
Lewin, Gary R.
中科院分区：
文献类型：
--
作者：
Heidenreich, Matthias;Lechner, Stefan G.;Lewin, Gary R.
使钾通道KCNQ4(K(V)7.4)失活的突变会导致人类和小鼠耳聋。KCNQ4除了在内耳的机械敏感毛细胞中表达外，还在听觉通路和三叉神经核团中表达，传递躯体感觉信息。我们现在已经从小鼠和人类的皮肤快速适应毛囊和触觉小体机械感受器的外周神经末梢中检测到KCNQ4。从Kcnq4(-/-)小鼠和携带KCNQ4突变的Kcnq4(-/-)小鼠的单一传入的电生理记录显示，在DFNA2型单基因显性人类听力损失中，机械敏感度提高，快速适应的频率响应改变，但D-Hair机械感受器神经元的慢适应或慢适应的频率响应不变。来自独立DFNA2家系的受试者在低频下进行振动触觉敏锐度测试时，表现优于年龄匹配的对照组受试者。这项工作描述了一种基因突变，它调节了小鼠和人类的触摸敏感性，并建立了KCNQ4作为快速适应迈斯纳和毛囊传入的子集的特定分子标记。
Mutations inactivating the potassium channel KCNQ4 (K(v)7.4) lead to deafness in humans and mice. In addition to its expression in mechanosensitive hair cells of the inner ear, KCNQ4 is found in the auditory pathway and in trigeminal nuclei that convey somatosensory information. We have now detected KCNQ4 in the peripheral nerve endings of cutaneous rapidly adapting hair follicle and Meissner corpuscle mechanoreceptors from mice and humans. Electrophysiological recordings from single afferents from Kcnq4(-/-) mice and mice carrying a KCNQ4 mutation found in DFNA2-type monogenic dominant human hearing loss showed elevated mechanosensitivity and altered frequency response of rapidly adapting, but not of slowly adapting nor of D-hair, mechanoreceptor neurons. Human subjects from independent DFNA2 pedigrees outperformed age-matched control subjects when tested for vibrotactile acuity at low frequencies. This work describes a gene mutation that modulates touch sensitivity in mice and humans and establishes KCNQ4 as a specific molecular marker for rapidly adapting Meissner and a subset of hair follicle afferents.