PDF(Pubmed)
Abstract：
KCNQ4 is a voltage-gated K+ channel was reported to distribute over the basolateral surface of type 1 vestibular hair cell and/or inner surface of calyx and heminode of the vestibular nerve connected to the type 1 vestibular hair cells of the inner ear. However, the precise localization of KCNQ4 is still controversial and little is known about the vestibular phenotypes caused by KCNQ4 dysfunction or the specific role of KCNQ4 in the vestibular organs. To investigate the role of KCNQ4 in the vestibular organ, 6-g hypergravity stimulation for 24 h, which represents excessive mechanical stimulation of the sensory epithelium, was applied to p.W277S Kcnq4 transgenic mice. KCNQ4 was detected on the inner surface of calyx of the vestibular afferent in transmission electron microscope images with immunogold labelling. Vestibular function decrease was more severe in the Kcnq4p.W277S/p.W277S mice than in the Kcnq4+/+ and Kcnq4+/p.W277S mice after the stimulation. The vestibular function loss was resulted from the loss of type 1 vestibular hair cells, which was possibly caused by increased depolarization duration. Retigabine, a KCNQ activator, prevented hypergravity-induced vestibular dysfunction and hair cell loss. Patients with KCNQ4 mutations also showed abnormal clinical vestibular function tests. These findings suggest that KCNQ4 plays an essential role in calyx and afferent of type 1 vestibular hair cell preserving vestibular function against excessive mechanical stimulation.
摘要：
据报道，KCNQ4是一种电压门控K通道，分布在1型前庭毛细胞的基底外侧表面和/或与内耳1型前庭毛细胞相连的前庭神经的花萼和半腹的内表面。然而,KCNQ4的精确定位仍存在争议,对KCNQ4功能障碍引起的前庭表型或KCNQ4在前庭器官中的具体作用知之甚少.探讨KCNQ4在前庭器官中的作用,6-g超重力刺激24小时，这代表了对感觉上皮的过度机械刺激，应用于p.W277SKcnq4转基因小鼠。在具有免疫金标记的透射电子显微镜图像中，在前庭传入的花萼的内表面上检测到KCNQ4。前庭功能下降在Kcnq4p中更为严重。W277S/p。W277S小鼠比在Kcnq4+/+和Kcnq4+/p。W277S小鼠刺激后。前庭功能的丧失是由于1型前庭毛细胞的丧失，这可能是由去极化持续时间增加引起的。Retigabine,KCNQ激活剂，防止超重力引起的前庭功能障碍和毛细胞损失。具有KCNQ4突变的患者也显示出异常的临床前庭功能测试。这些发现表明，KCNQ4在1型前庭毛细胞的花萼和传入中起着至关重要的作用，以保护前庭功能免受过度的机械刺激。
