Intercellular Ca2+ signalling in the adult mouse cochlea
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Key points Intercellular Ca2+ waves are increases in cytoplasmic Ca2+ levels that propagate between cells. Periodic Ca2+ waves have been linked to gene regulation and are thought to play a crucial role in the development of our hearing epithelium, the organ of Corti and the acquisition of hearing. We observed regular periodic intercellular Ca2+ waves in supporting cells of an ex vivo preparation of the adult mouse organ of Corti, and these waves were found to propagate independently of extracellular ATP and were inhibited by the gap junction blockers 1‐octanol and carbenoxolone. Our results establish that the existence of periodic Ca2+ waves in the organ of Corti is not restricted to the prehearing period. Abstract We have investigated wave‐like cytoplasmic calcium (Ca2+) signalling in an ex vivo preparation of the adult mouse organ of Corti. Two types of intercellular Ca2+ waves that differ in propagation distance and speed were observed. One type was observed to travel up to 100 μm with an average velocity of 7 μm/s. Such waves were initiated by local tissue damage in the outer hair cell region. The propagation distance was decreased when the purinergic receptor antagonists pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonic acid (PPADS; 50 μm) or suramin (150 μm) were added to the extracellular buffer. Immunocytochemical analysis and experiments with calcium indicator dyes showed that both P2X and P2Y receptors were present in supporting cells. A second class of waves identified to travel longitudinally along the organ of Corti propagated at a lower velocity of 1–3 μm/s. These ‘slow’ Ca2+ waves were particularly evident in the inner sulcus and Deiters’ cells. They travelled for distances of up to 500 μm. The slow Ca2+ signalling varied periodically (approximately one wave every 10 min) and was maintained for more than 3 h. The slow waves were not affected by apyrase, or by the P2 receptor agonists suramin (150 μm) or PPADS (50 μm) but were blocked by the connexin channel blockers octanol (1 mm) and carbenoxolone (100 μm). It is proposed that the observed Ca2+ waves might be a physiological response to a change in extracellular environment and may be involved in critical gene regulation activities in the supporting cells of the cochlea.
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Ex vivo cochlear calcium waves slow from an initial velocity of 10-15 μm/s with distance from the site of lesion.
“Similarly to those in living skin, ex vivo cochlear calcium waves slow from an initial velocity of 10–15 μm/s with distance from the site of lesion (13, 24).”
From Damage-evoked signals in cochlear neurons and supporting cells (2024) · cites this paper as [24]
The Results section, “Imaging Ca2+ spread in the in situ cochlea” (page unavailable), reports lesion-initiated calcium waves in the ex vivo cochlea, with average speeds of 6.5 ± 3.4 and 7.2 ± 3 μm/s. It does not report an initial speed of 10–15 μm/s or that the waves slow with distance from the lesion. (LLM, conf=0.85)
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Acoustic trauma increases ribbon number and size in outer hair cells of the mouse cochlea
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“The otic capsule preparation was adapted from the in situ cochlea preparation described in Sirko and colleagues, wherein the hemidissected head was placed in 2.5 mM K1 external solution on ice and the otic capsule excised from the temporal bone (Sirko et al., 2019).”
BackgroundMethodResultInfluentialDamage-evoked signals in cochlear neurons and supporting cells
Wood, M. B., Nowak, N., & Fuchs, P. A. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1361747 · Cited by 7 · see citing works
“Calcium imaging also has been used to characterize damage-evoked epithelial waves in cochlear explants (12, 13, 24, 25).”
BackgroundMethodInfluential
- Authors
- Sirko, P., Gale, J. E., & Ashmore, J. F.
- Affiliations
- University College London (GB)
- Corresponding author
- Ashmore, Jonathan F
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2018-11-22
- Volume
- 597
- Issue
- 1
- Pages
- 303-317
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC6312409
- OpenAlex
- W2896680006
- Cited by
- 34
- References
- 37
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 5 · 2022: 9 · 2021: 5 · 2020: 6 · 2019: 3
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Physiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (Ref 093084)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- intercellular calcium waves, organ of Corti, cochlear supporting cells, gap junctions, connexin channels, P2X receptors, P2Y receptors, purinergic signaling, Deiters' cells, outer hair cells, gene expression regulation, mouse cochlea, suramin
- MeSH terms
- Adenosine Triphosphate, Animals, Calcium, Cochlea, Female, Male, Mice, Inbred C57BL, Calcium Signaling
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