Spontaneous Activity of Cochlear Hair Cells Triggered by Fluid Secretion Mechanism in Adjacent Support Cells

Han Chin Wang, Chun Chieh Lin, Rocky Cheung, Yingxin Zhang-Hooks, Amit Agarwal, Graham Ellis-Davies, Jason Rock, Dwight E. Bergles

Research output: Contribution to journalArticle

Abstract

Spontaneous electrical activity of neurons in developing sensory systems promotes their maturation and proper connectivity. In the auditory system, spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from glia-like inner supporting cells (ISCs), facilitating maturation of central pathways before hearing onset. Here, we find that ATP stimulates purinergic autoreceptors in ISCs, triggering Cl- efflux and osmotic cell shrinkage by opening TMEM16A Ca2+-activated Cl- channels. Release of Cl- from ISCs also forces K+ efflux, causing transient depolarization of IHCs near ATP release sites. Genetic deletion of TMEM16A markedly reduces the spontaneous activity of IHCs and spiral ganglion neurons in the developing cochlea and prevents ATP-dependent shrinkage of supporting cells. These results indicate that supporting cells in the developing cochlea have adapted a pathway used for fluid secretion in other organs to induce periodic excitation of hair cells.

Original languageEnglish (US)
Pages (from-to)1348-1359
Number of pages12
JournalCell
Volume163
Issue number6
DOIs
StatePublished - Dec 3 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Wang, H. C., Lin, C. C., Cheung, R., Zhang-Hooks, Y., Agarwal, A., Ellis-Davies, G., Rock, J., & Bergles, D. E. (2015). Spontaneous Activity of Cochlear Hair Cells Triggered by Fluid Secretion Mechanism in Adjacent Support Cells. Cell, 163(6), 1348-1359. https://doi.org/10.1016/j.cell.2015.10.070