1. Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
2. Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
3. Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
4. Departments of Anesthesiology, Neurology and Physiology, Northwestern University Institute for Neurosciences, Chicago, Illinois 60611, USA
5. Departments of Neuroscience and Otolaryngology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
6. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
7. Laboratory for Molecular Medicine, Harvard-Partners Genome Center, Cambridge, Massachusetts 02139, USA
8. Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina 27705, USA
9. Matrix and Morphogenesis Unit, CDBRB, NIDCR, NIH, Bethesda, Maryland 20892, USA
10. These authors contributed equally to this work

Correspondence to: David P. Corey^1,2,10 Email: dcorey@hms.harvard.edu

Abstract

Mechanical deflection of the sensory hair bundles of receptor cells in the inner ear causes ion channels located at the tips of the bundle to open, thereby initiating the perception of sound. Although some protein constituents of the transduction apparatus are known, the mechanically gated transduction channels have not been identified in higher vertebrates. Here, we investigate TRP (transient receptor potential) ion channels as candidates and find one, TRPA1 (also known as ANKTM1), that meets criteria for the transduction channel. The appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label hair bundles, especially at their tips, and tip labelling disappears when the transduction apparatus is chemically disrupted. Inhibition of TRPA1 protein expression in zebrafish and mouse inner ears inhibits receptor cell function, as assessed with electrical recording and with accumulation of a channel-permeant fluorescent dye. TRPA1 is probably a component of the transduction channel itself.

1. Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
2. Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
3. Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
4. Departments of Anesthesiology, Neurology and Physiology, Northwestern University Institute for Neurosciences, Chicago, Illinois 60611, USA
5. Departments of Neuroscience and Otolaryngology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
6. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
7. Laboratory for Molecular Medicine, Harvard-Partners Genome Center, Cambridge, Massachusetts 02139, USA
8. Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina 27705, USA
9. Matrix and Morphogenesis Unit, CDBRB, NIDCR, NIH, Bethesda, Maryland 20892, USA
10. These authors contributed equally to this work

Correspondence to: David P. Corey^1,2,10 Email: dcorey@hms.harvard.edu

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.