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

David P. Corey*, Jaime Garcia-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, Duan Sun Zhang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

579 Scopus citations

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 transaction 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.

Original languageEnglish (US)
Pages (from-to)723-730
Number of pages8
JournalNature
Volume432
Issue number7018
DOIs
StatePublished - Dec 9 2004

Funding

Acknowledgements Authors’ contributions are listed in Supplementary Information. We thank C.-L. Chen and Q. Ma for assistance with in situ hybridization, N. Hopkins for zebrafish support and L. Stevens for laboratory administration. This work was supported by grants from NIH to N. Hopkins, S.-Y.L., J.G.-A., G.S.G.G., J.R.H. and D.P.C.; from the Mathers Foundation to D.P.C.; from the Howard Hughes Medical Institute (J.G.-A.); and from the Charles Dana Foundation to Q. Ma. P.G. was a Parker B. Francis Fellow in Pulmonary Medicine. J.G.-A., A.D., G.G., J.R.H. and H.L.R. were Associates, M.A.V. and K.K. are Associates, and D.P.C. is an Investigator of the Howard Hughes Medical Institute.

ASJC Scopus subject areas

  • General

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