Evidence map›Paper›PMID 40642832›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

LRRC8A Regulates Outer Hair Cell Volume and Electromotility and is Required for Hearing.

Shengnan Wang, Yuehui Xi, Qiaojun Fang, Sai Shi, Fei Wang, Fuyu Xian, Zhongyang Zhang, Yuxin Yang, Xishuo Jin, Xiaomin Wang and 6 more

Abstract read
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Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. LRRC8A Regulates Outer Hair Cell Volume and Electromotility and is Required for Hearing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Shengnan WangDepartment 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.
Yuehui XiShandong 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.
Qiaojun FangDepartment of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Sai ShiDepartment of Medical and Pharmaceutical Informatics, Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
Fei WangDepartment 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.
Fuyu XianDepartment 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.
Zhongyang ZhangDepartment 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.
Yuxin YangDepartment 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.
Xishuo JinDepartment 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.
Xiaomin WangDepartment 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.
Chen CaoDepartment 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.
Hailin ZhangDepartment 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.
Nikita GamperDepartment 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.
Zhigang XuShandong 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.
Haitao ShenLab of Pathology, Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
Ping LvDepartment 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.ORCID https://orcid.org/0000-0002-6271-8865

Funding

BBSRC International Partnering Award BB/R02104X/1National Key R&D Program of China 2024YFC2511104National Natural Science Foundation of China 32471181National Natural Science Foundation of China 82192861National Natural Science Foundation of China 82271178National Natural Science Foundation of China 82471615National Science Foundation for Young Scientists of China 82000986Natural Science Foundation of Hebei Province H2021206351Natural Science Foundation of Hebei Province H2022206551S&T Program of Hebei 216Z7701G
6 · The paper itself

Abstract

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-regulated anion channels (VRACs) are essential for OHC function. VRAC subunits are highly expressed in OHCs. Genetic deletion of leucin-rich repeat containing 8A (LRRC8A), the obligatory VRAC subunit, in hair cells results in hearing loss, whereas re-expressing LRRC8A in the cochlea restores hearing in LRRC8A-deficient mice. By employing patch-clamp 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-deficient 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.

Indexed as

Hair Cells, Auditory, OuterHearingMembrane ProteinsAnimalsCell SizeMiceMice, KnockoutLRRC8A protein, mouseMembrane Proteinscell volume regulationLRRC8outer hair cellsprestinVRAC

Identifiers

PMID40642832
PMCPMC12591118

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.