Yang, Y. orcid.org/0000-0001-5560-052X, Murtha, K., Climer, L.K. orcid.org/0000-0003-0236-1822 et al. (5 more authors) (2023) Oncomodulin regulates spontaneous calcium signalling and maturation of afferent innervation in cochlear outer hair cells. The Journal of Physiology, 601 (19). pp. 4291-4308. ISSN 0022-3751
Abstract
Cochlear outer hair cells (OHCs) are responsible for the exquisite frequency selectivity and sensitivity of mammalian hearing. During development, the maturation of OHC afferent connectivity is refined by coordinated spontaneous Ca2+ activity in both sensory and non-sensory cells. Calcium signalling in neonatal OHCs can be modulated by oncomodulin (OCM, β-parvalbumin), an EF-hand calcium-binding protein. Here, we investigated whether OCM regulates OHC spontaneous Ca2+ activity and afferent connectivity during development. Using a genetically encoded Ca2+ sensor (GCaMP6s) expressed in OHCs in wild-type (Ocm+/+) and Ocm knockout (Ocm−/−) littermates, we found increased spontaneous Ca2+ activity and upregulation of purinergic receptors in OHCs from Ocm−/− cochlea immediately following birth. The afferent synaptic maturation of OHCs was delayed in the absence of OCM, leading to an increased number of ribbon synapses and afferent fibres on Ocm−/− OHCs before hearing onset. We propose that OCM regulates the spontaneous Ca2+ signalling in the developing cochlea and the maturation of OHC afferent innervation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 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: | EF-hand calcium-binding protein; oncomodulin (OCM); outer Hair Cell (OHC); presynaptic ribbons; purinergic receptors; spontaneous calcium activity; voltage-gated calcium channels |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 07 Sep 2023 08:19 |
Last Modified: | 06 Nov 2023 09:20 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1113/jp284690 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:202996 |