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

• Published in: Cell 2015-12, Vol.163 (6), p.1348-1359
• Main Authors: Wang, Han Chin, Lin, Chun-Chieh, Cheung, Rocky, Zhang-Hooks, YingXin, Agarwal, Amit, Ellis-Davies, Graham, Rock, Jason, Bergles, Dwight E.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; Anoctamin-1; Chloride Channels - genetics; Chloride Channels - metabolism; Ear, Inner - cytology; Ear, Inner - growth & development; Ear, Inner - metabolism; Hair Cells, Auditory - cytology; Hair Cells, Auditory - metabolism; Labyrinth Supporting Cells - cytology; Labyrinth Supporting Cells - metabolism; Mice; Mice, Knockout; Potassium - metabolism; Rats; Rats, Sprague-Dawley; Spiral Ganglion - cytology; Spiral Ganglion - metabolism
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2015.10.070

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. [Display omitted] •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 Glia-like support cells in the developing cochlea use a fluid secretion pathway that causes cell shrinkage to trigger periodic excitation of inner hair cells.