| Title: |
A critical period of prehearing spontaneous Ca2+ spiking is required for hair-bundle maintenance in inner hair cells |
| Authors: |
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 |
| Publication Year: |
2023 |
| Collection: |
University of Sussex (US): Figshare |
| Subject Terms: |
calcium waves; development; hair cell; mechanoelectrical transduction; spontaneous action potentials; Animals; Hair Cells; Auditory; Inner; Action Potentials; Signal Transduction; Cochlea; Mammals |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
10779/uos.23495456.v1 |
| Availability: |
https://figshare.com/articles/journal_contribution/A_critical_period_of_prehearing_spontaneous_Ca2_spiking_is_required_for_hair-bundle_maintenance_in_inner_hair_cells/23495456 |
| Rights: |
CC BY 4.0 |
| Accession Number: |
edsbas.50C769F8 |
| Database: |
BASE |