Carlton, A.J. orcid.org/0000-0002-1054-3901, Jeng, J. orcid.org/0000-0002-6274-8597, Grandi, F.C. orcid.org/0000-0002-1303-6710 et al. (10 more authors) (2023) A critical period of prehearing spontaneous Ca2+ spiking is required for hair-bundle maintenance in inner hair cells. The EMBO Journal. e112118. ISSN 0261-4189
Abstract
Sensory-independent Ca2+ spiking regulates the development of mammalian sensory systems. In the immature cochlea, inner hair cells (IHCs) fire spontaneous Ca2+ action potentials (APs) that are generated either intrinsically or by intercellular Ca2+ waves in the nonsensory cells. The extent to which either or both of these Ca2+ signalling mechansims are required for IHC maturation is unknown. We find that intrinsic Ca2+ APs in IHCs, but not those elicited by Ca2+ waves, regulate the maturation and maintenance of the stereociliary hair bundles. Using a mouse model in which the potassium channel Kir2.1 is reversibly overexpressed in IHCs (Kir2.1-OE), we find that IHC membrane hyperpolarization prevents IHCs from generating intrinsic Ca2+ APs but not APs induced by Ca2+ waves. Absence of intrinsic Ca2+ APs leads to the loss of mechanoelectrical transduction in IHCs prior to hearing onset due to progressive loss or fusion of stereocilia. RNA-sequencing data show that pathways involved in morphogenesis, actin filament-based processes, and Rho-GTPase signaling are upregulated in Kir2.1-OE mice. By manipulating in vivo expression of Kir2.1 channels, we identify a “critical time period” during which intrinsic Ca2+ APs in IHCs regulate hair-bundle function.
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Copyright, Publisher and Additional Information: | © 2022 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | ||||||||||
Keywords: | calcium waves; development; hair cell; mechanoelectrical transduction; spontaneous action potentials | ||||||||||
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Institution: | The University of Sheffield | ||||||||||
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) | ||||||||||
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Depositing User: | Symplectic Sheffield | ||||||||||
Date Deposited: | 11 Jan 2023 10:56 | ||||||||||
Last Modified: | 11 Jan 2023 10:56 | ||||||||||
Published Version: | http://dx.doi.org/10.15252/embj.2022112118 | ||||||||||
Status: | Published online | ||||||||||
Publisher: | EMBO | ||||||||||
Refereed: | Yes | ||||||||||
Identification Number: | https://doi.org/10.15252/embj.2022112118 | ||||||||||
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