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Peer-reviewedCC BY 4.0Exploration

Triggered Calcium Lightning Programs Cochlear Development

  • Qiang Ma1
  • Hai‐Peng Wang2
  • Yu‐Meng Jiang1
  • Ke Lai1,3,4
  • Ming‐Xian Li1
  • Zhen Zhang1
  • Li‐Na Gong1
  • Jing‐Wei Lai1
  • Kai‐Ming Su1
  • Lu‐Yang Wang3,4
  • Hui Wang1,5
  • Shan‐Kai Yin1,5
2 more authors
  • Hao He1,2
  • Hai‐Bo Shi1,5
5 affiliations
  1. 1Department of Otorhinolaryngology Head & Neck Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China
  2. 2School of Biomedical Engineering Shanghai Jiao Tong University Shanghai China
  3. 3Program in Neurosciences and Mental Health SickKids Research Institute Toronto Canada
  4. 4Department of Physiology University of Toronto Toronto Canada
  5. 5Shanghai Key Laboratory of Sleep Disordered Breathing Shanghai China
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Abstract

Spontaneous calcium (Ca2+) waves play a critical role as internal stimuli in the early developing auditory system before the onset of sensory experiences. However, neither the spatiotemporal control of spontaneous Ca2+ waves nor their impacts on auditory development are well understood. Here we report that a lateral array of inner supporting cells (ISCs) beneath the inner hair cells displays a spontaneous ultra‐long, ultra‐fast, transient Ca2+ flash, termed “Ca2+ lightning”, which triggers a series of simultaneous bursts of Ca2+ waves in the whole cochlea, before the ear canal opening. The Ca2+ lightning margins the cochlear ISCs at different developmental stages that correspondingly exhibit different Ca2+ activities. Triggered by an ATP‐induced high‐level Ca2+ wave, the Ca2+ lightning rapidly propagates laterally into neighboring ISCs through the intricate interplay of the T‐type Ca2+ channel, Anoctamin 1 (Ano1) Ca2+‐activated Cl− channel and Connexin 26 (Cx26). The genetic deletion of Cav3.2, Ano1, or Cx26 abrogates Ca2+ lightning flashes and dysregulates cell development and functions in peripheral cochleae. We propose that cochlear Ca2+ lightning flashes orderly with Ca2+ waves together orchestrate the spatiotemporal maturation processes of the peripheral auditory system before the onset of hearing.

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Cite

BibTeXRIS
BibTeX
@article{ma2026triggered,
  title = {{Triggered Calcium Lightning Programs Cochlear Development}},
  author = {Qiang Ma and Hai‐Peng Wang and Yu‐Meng Jiang and Ke Lai and Ming‐Xian Li and Zhen Zhang and Li‐Na Gong and Jing‐Wei Lai and Kai‐Ming Su and Lu‐Yang Wang and Hui Wang and Shan‐Kai Yin and Hao He and Hai‐Bo Shi},
  journal = {Exploration},
  year = {2026},
  month = jul,
  doi = {10.1002/exp2.70205},
  url = {https://doi.org/10.1002/exp2.70205},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Triggered Calcium Lightning Programs Cochlear Development
AU  - Qiang Ma
AU  - Hai‐Peng Wang
AU  - Yu‐Meng Jiang
AU  - Ke Lai
AU  - Ming‐Xian Li
AU  - Zhen Zhang
AU  - Li‐Na Gong
AU  - Jing‐Wei Lai
AU  - Kai‐Ming Su
AU  - Lu‐Yang Wang
AU  - Hui Wang
AU  - Shan‐Kai Yin
AU  - Hao He
AU  - Hai‐Bo Shi
PY  - 2026
DA  - 2026/07/26
JO  - Exploration
DO  - 10.1002/exp2.70205
UR  - https://doi.org/10.1002/exp2.70205
AB  - Spontaneous calcium (Ca2+) waves play a critical role as internal stimuli in the early developing auditory system before the onset of sensory experiences. However, neither the spatiotemporal control of spontaneous Ca2+ waves nor their impacts on auditory development are well understood. Here we report that a lateral array of inner supporting cells (ISCs) beneath the inner hair cells displays a spontaneous ultra‐long, ultra‐fast, transient Ca2+ flash, termed “Ca2+ lightning”, which triggers a series of simultaneous bursts of Ca2+ waves in the whole cochlea, before the ear canal opening. The Ca2+ lightning margins the cochlear ISCs at different developmental stages that correspondingly exhibit different Ca2+ activities. Triggered by an ATP‐induced high‐level Ca2+ wave, the Ca2+ lightning rapidly propagates laterally into neighboring ISCs through the intricate interplay of the T‐type Ca2+ channel, Anoctamin 1 (Ano1) Ca2+‐activated Cl− channel and Connexin 26 (Cx26). The genetic deletion of Cav3.2, Ano1, or Cx26 abrogates Ca2+ lightning flashes and dysregulates cell development and functions in peripheral cochleae. We propose that cochlear Ca2+ lightning flashes orderly with Ca2+ waves together orchestrate the spatiotemporal maturation processes of the peripheral auditory system before the onset of hearing.
SN  - 2766-8509
SN  - 2766-2098
ER  -