| Title: |
A critical period of prehearing spontaneous Ca2+ spiking is required for hair-bundle maintenance in inner hair cells |
| Authors: |
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; Marcotti, Walter |
| Publisher Information: |
EMBO |
| Publication Year: |
2023 |
| Collection: |
University of Sussex: Sussex Research Online |
| 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 |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0261-4189 |
| Relation: |
http://sro.sussex.ac.uk/id/eprint/111494/1/The%20EMBO%20Journal%20-%202023%20-%20Carlton%20-%20A%20critical%20period%20of%20prehearing%20spontaneous%20Ca2%20%20spiking%20is%20required%20for%20hair%E2%80%90bundle.pdf; 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 |
| DOI: |
10.15252/embj.2022112118 |
| Availability: |
http://sro.sussex.ac.uk/id/eprint/111494/; http://sro.sussex.ac.uk/id/eprint/111494/1/The%20EMBO%20Journal%20-%202023%20-%20Carlton%20-%20A%20critical%20period%20of%20prehearing%20spontaneous%20Ca2%20%20spiking%20is%20required%20for%20hair%E2%80%90bundle.pdf; https://doi.org/10.15252/embj.2022112118 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.3B742630 |
| Database: |
BASE |