A critical period of prehearing spontaneous Ca2+ spiking is required for hair-bundle maintenance in inner hair cells

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Carlton, Adam J, Jeng, Jing-Yi, Grandi, Fiorella C, De Faveri, Francesca, Ceriani, Federico, De Tomasi, Lara, Underhill, Anna, Johnson, Stuart L, Legan, Kevin P, Kros, Corne J, Richardson, Guy P, Mustapha, Mirna and Marcotti, Walter (2023) A critical period of prehearing spontaneous Ca2+ spiking is required for hair-bundle maintenance in inner hair cells. EMBO Journal, 42 (4). e112118. ISSN 0261-4189

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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.

Item Type: Article
Keywords: calcium waves, development, hair cell, mechanoelectrical transduction, spontaneous action potentials, Animals, Hair Cells, Auditory, Inner, Action Potentials, Signal Transduction, Cochlea, Mammals
Schools and Departments: School of Life Sciences > Neuroscience
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 28 Mar 2023 12:36
Last Modified: 28 Mar 2023 12:45
URI: http://sro.sussex.ac.uk/id/eprint/111494

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