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However, most studies to date have focused on the cochlea, so little is known about the distribution and uptake of gentamicin by the counterpart of the auditory system, specifically\u00a0vestibular hair cells (HCs). Here, with a combination of in vivo and in vitro approaches, we used a gentamicin\u2010Texas Red (GTTR) conjugate to investigate the mechanisms of gentamicin vestibulotoxicity in the developing mammalian utricular HCs.\u00a0In vivo, GTTR fluorescence was concentrated in the apical cytoplasm and the cellular membrane of neonatal utricular HCs, but scarce in the nucleus of HCs and supporting cells. Quantitative analysis showed the GTTR uptake by striolar HCs was significantly higher than that in the extrastriola. In addition, the GTTR fluorescence intensity in the striola was increased gradually from 1 to 8 days, peaking at 8\u20139 days postnatally. In vitro, utricle explants were incubated with GTTR and candidate uptake conduits, including mechanotransduction (MET) channels and endocytosis in the HC, were inhibited separately. GTTR uptake by HCs could be inhibited by quinine, a blocker of MET channels, under both normal and stressed conditions. Meanwhile, endocytic inhibition only reduced GTTR uptake in the CoCl<jats:sub>2<\/jats:sub> hypoxia model. In sum, the maturation of MET channels mediated uptake of GTTR into vestibular HCs. Under stressed conditions, MET channels play a pronounced role, manifested by channel\u2010dependent stress enhanced GTTR permeation, while endocytosis participates in GTTR entry in a more selective manner.<\/jats:p>","DOI":"10.1002\/jcp.30228","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T02:52:09Z","timestamp":1608864729000},"page":"5235-5252","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hair cell uptake of gentamicin in the developing mouse utricle"],"prefix":"10.1002","volume":"236","author":[{"given":"Xiaoqing","family":"Qian","sequence":"first","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology Eye &amp; ENT Hospital, Fudan University Shanghai China"},{"name":"NHC Key Laboratory of Hearing Medicine (Fudan University) Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyu","family":"He","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology Eye &amp; ENT Hospital, Fudan University Shanghai China"},{"name":"NHC Key Laboratory of Hearing Medicine (Fudan University) Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanmei","family":"Wang","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology Eye &amp; ENT Hospital, Fudan University Shanghai China"},{"name":"NHC Key Laboratory of Hearing Medicine (Fudan University) Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binjun","family":"Chen","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology Eye &amp; ENT Hospital, Fudan University Shanghai China"},{"name":"NHC Key Laboratory of Hearing Medicine (Fudan University) Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisa","family":"Hetrick","sequence":"additional","affiliation":[{"name":"Research Service, VA Loma Linda Healthcare System Loma Linda California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunfu","family":"Dai","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology Eye &amp; ENT Hospital, Fudan University Shanghai China"},{"name":"NHC Key Laboratory of Hearing Medicine (Fudan University) Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanglu","family":"Chi","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology Eye &amp; ENT Hospital, Fudan University Shanghai China"},{"name":"NHC Key Laboratory of Hearing Medicine (Fudan University) Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0207-5367","authenticated-orcid":false,"given":"Hongzhe","family":"Li","sequence":"additional","affiliation":[{"name":"Research Service, VA Loma Linda Healthcare System Loma Linda California USA"},{"name":"Department of Otolaryngology\u2014Head and Neck Surgery Loma Linda University School of Medicine Loma Linda California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2889-9375","authenticated-orcid":false,"given":"Dongdong","family":"Ren","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology Eye &amp; ENT Hospital, Fudan University Shanghai China"},{"name":"NHC Key Laboratory of Hearing Medicine (Fudan University) Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019183"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022347"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08636.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1L001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1288\/00005537-198112000-00001"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-012-0337-0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2013.867484"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00453932"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.84.1.139"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.moo.0000186799.45377.63"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2005.11.011"},{"issue":"9","key":"e_1_2_9_13_1","first-page":"601","article-title":"Ototoxicity of kanamycin studied day by day. 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