Jeng, J., Carlton, A.J. orcid.org/0000-0002-1054-3901, Johnson, S.L. et al. (4 more authors) (2021) Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea. The Journal of Physiology, 599 (1). pp. 269-287. ISSN 0022-3751
Abstract
Inner hair cells (IHCs) are the primary sensory receptors of the mammalian cochlea, transducing acoustic information into electrical signals that are relayed to the afferent neurons. Functional changes in IHCs are a potential cause of age‐related hearing loss. Here, we have investigated the functional characteristics of IHCs from early‐onset hearing loss mice harbouring the allele Cdh23ahl (C57BL/6J and C57BL/6NTac), from late‐onset hearing loss mice (C3H/HeJ), and from mice corrected for the Cdh23ahl mutation (C57BL/6NTacCdh23+) with an intermediate hearing phenotype. There was no significant loss of IHCs in the 9–12 kHz cochlear region up to at least 15 months of age, but their surface area decreased progressively by 30–40% starting from ∼6 months of age. Although the size of the BK current decreased with age, IHCs retained a normal KCNQ4 current and resting membrane potential. These basolateral membrane changes were most severe for C57BL/6J and C57BL/6NTac, less so for C57BL/6NTacCdh23+ and minimal or absent in C3H/HeJ mice. We also found that lateral olivocochlear (LOC) efferent fibres re‐form functional axon‐somatic connections with aged IHCs, but this was seen only sporadically in C3H/HeJ mice. The efferent post‐synaptic SK2 channels appear prior to the establishment of the efferent contacts, suggesting that IHCs may play a direct role in re‐establishing the LOC‐IHC synapses. Finally, we showed that the size of the mechanoelectrical transducer (MET) current from IHCs decreased significantly with age in mice harbouring the Cdh23ahl allele but not in C57BL/6NTacCdh23+mice, indicating that the MET apparatus directly contributes to the progression of age‐related hearing loss.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | auditory brainstem responses; C3H/HeJ mice; C57BL/6 mice; cadherin 23; cochlea; hair cells; hearing loss; mechanoelectrical transduction; olivocochlear efferent fibres; potassium currents |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 102892/Z/13/Z BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/T004991/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 28 Jan 2021 14:47 |
Last Modified: | 28 Jan 2021 14:47 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1113/jp280256 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:169668 |