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PMID: 15483558 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Nature ·Vol. 432 ·No. 7018 ·2004-12-09 ·Pages 723-30

Corey DP, García-Añoveros J, Holt JR, Kwan KY, Lin SY, Vollrath MA, Amalfitano A, Cheung EL, Derfler BH, Duggan A, Géléoc GS, Gray PA, Hoffman MP, Rehm HL, Tamasauskas D, Zhang DS

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.

MeSH Terms
Adenoviridae/genetics Animals Animals, Newborn Antibodies/immunology Ear, Inner/metabolism Gene Expression Regulation, Developmental Hair Cells, Auditory/metabolism Hearing/physiology In Situ Hybridization Ion Channels/biosynthesis,genetics,immunology,metabolism Mechanotransduction, Cellular/physiology Mice Oligonucleotides/genetics,metabolism RNA, Messenger/genetics,metabolism RNA, Small Interfering/genetics,metabolism Rana catesbeiana TRPA1 Cation Channel Transient Receptor Potential Channels Vertebrates/metabolism Zebrafish/metabolism Zebrafish Proteins/biosynthesis,genetics,immunology,metabolism
Chemicals
Antibodies Ion Channels Oligonucleotides RNA, Messenger RNA, Small Interfering TRPA1 Cation Channel Transient Receptor Potential Channels Trpa1 protein, mouse Zebrafish Proteins trpa1a protein, zebrafish
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Corey David P
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. dcorey@hms.harvard.edu
García-Añoveros Jaime
Holt Jeffrey R
Kwan Kelvin Y
Lin Shuh-Yow
Vollrath Melissa A
Amalfitano Andrea
Cheung Eunice L-M
Derfler Bruce H
Duggan Anne
Géléoc Gwénaëlle S G
Gray Paul A
Hoffman Matthew P
Rehm Heidi L
Tamasauskas Daniel
Zhang Duan-Sun
Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
Published
2004-12-09
Epub
2004-00-13
Pages
723-30
Language
English
Region
England
NLM ID
0410462
Subset
IM
Corrections
CommentIn
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