Jeng, J-Y;
Johnson, SL;
Carlton, AJ;
De Tomasi, L;
Goodyear, RJ;
De Faveri, F;
Furness, DN;
... Marcotti, W; + view all
(2020)
Age-related changes in the biophysical and morphological characteristics of mouse cochlear outer hair cells.
Journal of Physiology
, 598
(18)
pp. 3891-3910.
10.1113/JP279795.
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Abstract
Outer hair cells (OHCs) are electromotile sensory receptors that provide sound amplification within the mammalian cochlea. Although OHCs appear susceptible to ageing, the progression of the pathophysiological changes in these cells is still poorly understood. By using mouse strains with a different progression of hearing loss (C57BL/6J, C57BL/6NTac, C57BL/6NTacCdh23+, C3H/HeJ), we have identified morphological, physiological and molecular changes in ageing OHCs (9–12 kHz cochlear region). We show that by 6 months of age, OHCs from all strains underwent a reduction in surface area, which was not a sign of degeneration. Although the ageing OHCs retained a normal basolateral membrane protein profile, they showed a reduction in the size of the K+ current and non‐linear capacitance, a readout of prestin‐dependent electromotility. Despite these changes, OHCs have a normal Vm and retain the ability to amplify sound, as distortion product otoacoustic emission thresholds were not affected in aged, good‐hearing mice (C3H/HeJ, C57BL/6NTacCdh23+). The loss of afferent synapses was present in all strains at 15 months. The number of efferent synapses per OHCs, defined as postsynaptic SK2 puncta, was reduced in aged OHCs of all strains apart from C3H mice. Several of the identified changes occurred in aged OHCs from all mouse strains, thus representing a general trait in the pathophysiological progression of age‐related hearing loss, possibly aimed at preserving functionality. We have also shown that the mechanoelectrical transduction (MET) current from OHCs of mice harbouring the Cdh23ahl allele is reduced with age, highlighting the possibility that changes in the MET apparatus could play a role in cochlear ageing.
| Type: | Article |
|---|---|
| Title: | Age-related changes in the biophysical and morphological characteristics of mouse cochlear outer hair cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1113/JP279795 |
| Publisher version: | http://dx.doi.org/10.1113/JP279795 |
| Language: | English |
| 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, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | cochlea, electromotility, hearing loss, ion channels, mechanoelectrical transduction, mouse, OHCs, PRODUCT OTOACOUSTIC EMISSIONS, HEARING-LOSS, OLIVOCOCHLEAR INNERVATION, DEVELOPMENTAL EXPRESSION, VOLTAGE SENSOR, MOTOR PROTEIN, PRESTIN, INNER, PATHOLOGY, MODEL |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10112361 |
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