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

• Published in: Scientific reports Vol. 14; no. 1; pp. 15260 - 17
• Main Authors: Hong, Hansol, Koo, Eun Ji, Park, Yesai, Song, Gabae, Joo, Sun Young, Kim, Jung Ah, Gee, Heon Yung, Jung, Jinsei, Park, Kangyoon, Han, Gyu Cheol, Choie, Jae Young, Kim, Sung Huhn
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.07.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/2586; 631/378/2617; 631/378/3917; 631/378/87; Animals; Carbamates - pharmacology; Cell surface; Channel gating; Depolarization; Genotype & phenotype; Hair; Hair cells; Hair Cells, Vestibular - metabolism; Hair Cells, Vestibular - pathology; Hearing loss; Hearing protection; Humanities and Social Sciences; Hypergravity; Inner ear; KCNQ Potassium Channels - genetics; KCNQ Potassium Channels - metabolism; KCNQ4 protein; Labeling; Localization; Mechanical properties; Mechanical stimuli; Medical schools; Medicine; Mice; Mice, Transgenic; multidisciplinary; Mutation; Otolaryngology; Phenotypes; Phenylenediamines - pharmacology; Potassium channels (voltage-gated); Science; Science (multidisciplinary); Sensory epithelium; Sensory neurons; Transgenic animals; Transgenic mice; University colleges; Vestibular nerve; Vestibular system; Vestibule, Labyrinth - metabolism; Vestibule, Labyrinth - pathology; Vestibule, Labyrinth - physiopathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-66115-9

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 p.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.