Cell
Volume 163, Issue 6, 3 December 2015, Pages 1348-1359
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Article
Spontaneous Activity of Cochlear Hair Cells Triggered by Fluid Secretion Mechanism in Adjacent Support Cells

https://doi.org/10.1016/j.cell.2015.10.070Get rights and content
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Highlights

  • Inner supporting cells (ISCs) in the developing cochlea express TMEM16A Cl channels

  • Spontaneous currents in ISCs reflect purinergic receptor-mediated gating of TMEM16A

  • Cl efflux through TMEM16A induces K+ release, which depolarizes inner hair cells

  • Spontaneous activity of hair cells and ganglion neurons is reduced in Tmem16a KO mice

Summary

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.

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Present address: Department of Chemistry and Biochemistry, University of California, Los Angeles, 611 Charles E Young Dr East, Boyer Hall Room 456, Los Angeles, CA 90095, USA