{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:58:48Z","timestamp":1773817128696,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"41","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC2511104"],"award-info":[{"award-number":["2024YFC2511104"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32471181"],"award-info":[{"award-number":["32471181"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471615"],"award-info":[{"award-number":["82471615"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82192861"],"award-info":[{"award-number":["82192861"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271178"],"award-info":[{"award-number":["82271178"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2022206551"],"award-info":[{"award-number":["H2022206551"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2021206351"],"award-info":[{"award-number":["H2021206351"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Damage to the cochlear outer hair cell (OHC) is a major cause of deafness in mammals. OHCs amplify the auditory signals to enhance the sensitivity and sound frequency selectivity of the auditory system. However, detailed mechanisms underlying functional OHC regulation remain unclear. Here, it is demonstrated that volume\u2010regulated anion channels (VRACs) are essential for OHC function. VRAC subunits are highly expressed in OHCs. Genetic deletion of leucin\u2010rich repeat containing 8A (LRRC8A), the obligatory VRAC subunit, in hair cells results in hearing loss, whereas re\u2010expressing LRRC8A in the cochlea restores hearing in LRRC8A\u2010deficient mice. By employing patch\u2010clamp electrophysiology, it is shown that VRAC in OHCs is activated by hypotonicity and is involved in regulating cell volume. Furthermore, the nonlinear capacitance (NLC), a measure of electromotility, is decreased in the OHCs from LRRC8A\u2010deficient mice. Therefore, LRRC8A deficiency compromises electromotility of OHCs and impairs signal amplification. In conclusion, the findings highlight the essential role of VRAC in OHC electromotility and its necessity for auditory function.<\/jats:p>","DOI":"10.1002\/advs.202410477","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T09:35:26Z","timestamp":1752226526000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["LRRC8A Regulates Outer Hair Cell Volume and Electromotility and is Required for Hearing"],"prefix":"10.1002","volume":"12","author":[{"given":"Shengnan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuehui","family":"Xi","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education School of Life Sciences Shandong University  Qingdao Shandong 266237 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaojun","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University  Hefei 230601 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Medical and Pharmaceutical Informatics Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuyu","family":"Xian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xishuo","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikita","family":"Gamper","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"},{"name":"Faculty of Biological Sciences School of Biomedical Sciences University of Leeds  Leeds LS2 9JT UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Xu","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education School of Life Sciences Shandong University  Qingdao Shandong 266237 China"},{"name":"Department of Otolaryngology Head and Neck Surgery the First Hospital of Lanzhou University  Lanzhou Gansu 730000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitao","family":"Shen","sequence":"additional","affiliation":[{"name":"Lab of Pathology Hebei Medical University  Shijiazhuang Hebei 050017 China"},{"name":"Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation Affiliated Hospital of Hebei University  Baoding Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6271-8865","authenticated-orcid":false,"given":"Ping","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The Key Laboratory of Neural and Vascular Biology Ministry of Education The Key Laboratory of New Drug Pharmacology and Toxicology The Hebei Collaboration Innovation Center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric Disease Hebei Medical University  Shijiazhuang Hebei 050017 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1177\/014556139707600309"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(83)90136-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-12-04575.1992"},{"key":"e_1_2_9_4_1","volume":"9","author":"Ashmore J.","year":"2019","journal-title":"Outer Hair Cells Electromotility"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35012009"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2007"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1385\/CBB:41:2:233"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1998.78.1.247"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107596"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/330066a0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1992.72.4.1037"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.29"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctm.2018.07.005"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2016.05.002"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0134-y"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1252826"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.024"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.031"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.06.015"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6107(97)00021-7"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.341bw.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400020200"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1561-8"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2019-0189"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-015-1781-6"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04353-y"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02664-0"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20051034"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-007-9004-5"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0791n.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.008840"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.118.015917"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP274795"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107436"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20551"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20632"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3109\/00016489709117775"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/MLG.0b013e3181788d72"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.5.2.14310"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade9931"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201592409"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01059"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045453"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2004.03.020"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-011-9708-z"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4545826"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2021.108376"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217891120"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4548-05.2006"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1060939"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.07.034"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04152-4"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27915-z"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00873.x"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.76754"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00869.2014"},{"key":"e_1_2_9_57_1","volume":"25","author":"Guo J. Y.","year":"2018","journal-title":"J. Vis. Exp."},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2005.03.030"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202410477","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:58:27Z","timestamp":1762423107000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202410477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,11]]},"references-count":58,"journal-issue":{"issue":"41","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/advs.202410477"],"URL":"https:\/\/doi.org\/10.1002\/advs.202410477","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,11]]},"assertion":[{"value":"2024-08-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10477"}}