TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells

David P. Corey (), Jaime García-Añoveros, Jeffrey R. Holt, Kelvin Y. Kwan, Shuh-Yow Lin, Melissa A. Vollrath, Andrea Amalfitano, Eunice L.-M. Cheung, Bruce H. Derfler, Anne Duggan, Gwénaëlle S. G. Géléoc, Paul A. Gray, Matthew P. Hoffman, Heidi L. Rehm, Daniel Tamasauskas and Duan-Sun Zhang
Additional contact information
David P. Corey: Harvard Medical School
Jaime García-Añoveros: Northwestern University Institute for Neurosciences
Jeffrey R. Holt: University of Virginia School of Medicine
Kelvin Y. Kwan: Harvard Medical School
Shuh-Yow Lin: Harvard Medical School
Melissa A. Vollrath: Harvard Medical School
Andrea Amalfitano: Duke University Medical Center
Eunice L.-M. Cheung: Harvard Medical School
Bruce H. Derfler: Harvard Medical School
Anne Duggan: Northwestern University Institute for Neurosciences
Gwénaëlle S. G. Géléoc: University of Virginia School of Medicine
Paul A. Gray: Harvard Medical School
Matthew P. Hoffman: Matrix and Morphogenesis Unit, CDBRB, NIDCR, NIH
Heidi L. Rehm: Harvard-Partners Genome Center
Daniel Tamasauskas: Harvard Medical School
Duan-Sun Zhang: Harvard Medical School

Nature, 2004, vol. 432, issue 7018, 723-730

Abstract: 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.

Date: 2004
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DOI: 10.1038/nature03066

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