The EMBO Journal - 2023 - Carlton - A critical period of prehearing spontaneous Ca2 spiking is required for hair%E2%80%90bundle.pdf (17.65 MB)
A critical period of prehearing spontaneous Ca2+ spiking is required for hair-bundle maintenance in inner hair cells
journal contributionposted on 2023-06-15, 15:44 authored by Adam J Carlton, Jing-Yi Jeng, Fiorella C Grandi, Francesca De Faveri, Federico Ceriani, Lara De Tomasi, Anna Underhill, Stuart L Johnson, Kevin P Legan, Corne Kros, Guy Richardson, Mirna Mustapha, Walter Marcotti
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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