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

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.

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Figure 1: Expression of TRPA1 in the mouse inner ear.
Figure 2: Antibody labelling of TRPA1 in bullfrog and mouse inner ears.
Figure 3: Redistribution of TRPA1 label upon disruption of the transduction apparatus.
Figure 4: Inhibition of transduction in zebrafish by morpholinos.
Figure 5: Inhibition of transduction in mouse with adenoviruses encoding siRNAs.

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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.

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Correspondence to David P. Corey.

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Contains Supplementary Figures 1–4, as well as supplementary methods and details of author’s contributions. (PDF 862 kb)

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Corey, D., García-Añoveros, J., Holt, J. et al. TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature 432, 723–730 (2004). https://doi.org/10.1038/nature03066

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