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前庭毛细胞在 KCNQ4 功能障碍的小鼠中更容易受到过度加速损伤的影响。

Vestibular hair cells are more prone to damage by excessive acceleration insult in the mouse with KCNQ4 dysfunction.

机构信息

Department of Otorhinolaryngology, Won-Sang Lee Institute for Hearing Loss, Yonsei University College of Medicine and Graduate School of Medicine, Seoul, Republic of Korea.

Department of Otorhinolaryngology, Gachon University College of Medicine, Incheon, Republic of Korea.

出版信息

Sci Rep. 2024 Jul 3;14(1):15260. doi: 10.1038/s41598-024-66115-9.

DOI:10.1038/s41598-024-66115-9
PMID:38956136
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11219875/
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 Kcnq4 mice than in the Kcnq4 and Kcnq4 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

KCNQ4 是一种电压门控钾通道，据报道分布于前庭毛细胞 1 型的基底外侧表面和/或前庭神经的内表面和连接内耳 1 型前庭毛细胞的壶腹和纤毛。然而，KCNQ4 的精确定位仍存在争议，对于 KCNQ4 功能障碍引起的前庭表型或 KCNQ4 在前庭器官中的特定作用知之甚少。为了研究 KCNQ4 在前庭器官中的作用，应用 6-g 超重力刺激 24 小时，这代表对感觉上皮的过度机械刺激，对 p.W277S Kcnq4 转基因小鼠进行了处理。用免疫金标记在透射电镜图像上检测到 KCNQ4 在前庭传入神经的内表面。刺激后，Kcnq4 小鼠的前庭功能下降比 Kcnq4 和 Kcnq4 小鼠更严重。前庭功能丧失是由于 1 型前庭毛细胞的丧失引起的，这可能是由于去极化持续时间的增加所致。KCNQ 激活剂 retigabine 可预防超重力诱导的前庭功能障碍和毛细胞丧失。KCNQ4 突变患者也表现出异常的临床前庭功能测试。这些发现表明，KCNQ4 在保持前庭功能方面对 1 型前庭毛细胞的壶腹和传入纤维起着重要作用，以抵抗过度的机械刺激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/97e59bd7ca1b/41598_2024_66115_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/32a32b9083e3/41598_2024_66115_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/e33a6392bb32/41598_2024_66115_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/78e11b358b79/41598_2024_66115_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/a8dca1a6c5b1/41598_2024_66115_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/97e59bd7ca1b/41598_2024_66115_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/32a32b9083e3/41598_2024_66115_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/fb98ec0808db/41598_2024_66115_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/770823510225/41598_2024_66115_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/b4c70bc3bfed/41598_2024_66115_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/9c7519a8d4e5/41598_2024_66115_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/e33a6392bb32/41598_2024_66115_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/78e11b358b79/41598_2024_66115_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/a8dca1a6c5b1/41598_2024_66115_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/11219875/97e59bd7ca1b/41598_2024_66115_Fig9_HTML.jpg

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本文引用的文献

1
Changes in metabolism and vestibular function depend on gravitational load in mice.代谢和前庭功能的变化取决于小鼠的重力负荷。
J Appl Physiol (1985). 2023 Jan 1;134(1):10-17. doi: 10.1152/japplphysiol.00555.2022. Epub 2022 Nov 17.
2
outer hair cell gene editing ameliorates progressive hearing loss in dominant-negative murine model.外毛细胞基因编辑可改善显性负性小鼠模型的进行性听力损失。
Theranostics. 2022 Feb 28;12(5):2465-2482. doi: 10.7150/thno.67781. eCollection 2022.
3
Hypergravity-induced malfunction was moderated by the regulation of NMDA receptors in the vestibular nucleus.
超重力诱导的故障通过前庭核内 NMDA 受体的调节得到缓解。
Sci Rep. 2021 Aug 31;11(1):17420. doi: 10.1038/s41598-021-97050-8.
4
Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss.激活KCNQ4作为治疗听力损失的一种治疗策略。
Int J Mol Sci. 2021 Mar 2;22(5):2510. doi: 10.3390/ijms22052510.
5
K Accumulation and Clearance in the Calyx Synaptic Cleft of Type I Mouse Vestibular Hair Cells.I 型小鼠前庭毛细胞壶腹突触裂中的 K 积累和清除。
Neuroscience. 2020 Feb 1;426:69-86. doi: 10.1016/j.neuroscience.2019.11.028. Epub 2019 Dec 14.
6
Rare KCNQ4 variants found in public databases underlie impaired channel activity that may contribute to hearing impairment.在公共数据库中发现的罕见 KCNQ4 变体导致通道活性受损，这可能导致听力损伤。
Exp Mol Med. 2019 Aug 21;51(8):1-12. doi: 10.1038/s12276-019-0300-9.
7
Vestibular evoked myogenic potentials in practice: Methods, pitfalls and clinical applications.实践中的前庭诱发肌源性电位：方法、陷阱与临床应用
Clin Neurophysiol Pract. 2019 Feb 26;4:47-68. doi: 10.1016/j.cnp.2019.01.005. eCollection 2019.
8
Accumulation of K in the synaptic cleft modulates activity by influencing both vestibular hair cell and calyx afferent in the turtle.突触间隙中钾离子的积累通过影响海龟的前庭毛细胞和杯状传入神经来调节活动。
J Physiol. 2017 Feb 1;595(3):777-803. doi: 10.1113/JP273060. Epub 2016 Nov 4.
9
Discrepancies between video head impulse and caloric tests in patients with enlarged vestibular aqueduct.大前庭导水管综合征患者视频头脉冲试验与冷热试验结果的差异
Laryngoscope. 2017 Apr;127(4):921-926. doi: 10.1002/lary.26122. Epub 2016 Jul 4.
10
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Hear Res. 2016 Aug;338:40-51. doi: 10.1016/j.heares.2016.01.015. Epub 2016 Feb 4.