Spontaneous Activity of Cochlear Hair Cells Triggered by Fluid Secretion Mechanism in Adjacent Support Cells.
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 Ca(2+)-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.
1 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, WBSB 1001, Baltimore, MD 21205, USA.
2 Department of Neuroscience, Mount Sinai School of Medicine, One Gustave Levy Place Box 1065, New York, NY 10029, USA.
3 Department of Anatomy, University of California, San Francisco, 513 Parnassus Ave, Box 0452, San Francisco, CA 94143, USA.
4 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, WBSB 1001, Baltimore, MD 21205, USA; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.