Login / Signup

A critical period of prehearing spontaneous Ca 2+ spiking is required for hair-bundle maintenance in inner hair cells.

Adam J CarltonJing-Yi JengFiorella Carla GrandiFrancesca De FaveriFederico CerianiLara De TomasiAnna UnderhillStuart L JohnsonKevin P LeganCorné J KrosGuy P RichardsonMirna MustaphaWalter Marcotti
Published in: The EMBO journal (2023)
Sensory-independent Ca 2+ spiking regulates the development of mammalian sensory systems. In the immature cochlea, inner hair cells (IHCs) fire spontaneous Ca 2+ action potentials (APs) that are generated either intrinsically or by intercellular Ca 2+ waves in the nonsensory cells. The extent to which either or both of these Ca 2+ signalling mechansims are required for IHC maturation is unknown. We find that intrinsic Ca 2+ APs in IHCs, but not those elicited by Ca 2+ 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 Ca 2+ APs but not APs induced by Ca 2+ waves. Absence of intrinsic Ca 2+ 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 Ca 2+ APs in IHCs regulate hair-bundle function.
Keyphrases