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

Autor: 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, Corné J, Richardson, Guy P, Mustapha, Mirna, Marcotti, Walter
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Zdroj: EMBO Journal; Feb2023, Vol. 42 Issue 4, p1-20, 20p
Abstrakt: 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. Synopsis: Immature inner hair cells (IHCs) generate spontaneous Ca2+ action potentials (APs) that are triggered either intrinsically or by intercellular Ca2+ waves in the nonsensory cells. This study shows that the absence of intrinsic APs blocks the maturation of the mechanoelectrical transducer apparatus. Overexpression of Kir2.1 potassium channels in IHCs prevents intrinsic APs but not APs induced by Ca2+ waves.Absence of intrinsic APs in IHCs causes them to lose mechanoelectrical transduction before the age of hearing onset.Intrinsic APs are required over a defined time window during prehearing development to regulate the maturation and maintenance of stereociliary hair bundles in IHCs. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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