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; Duan-Sun Zhang

doi:10.1038/nature03066

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

Nature. 2004 Dec 9;432(7018):723-30. doi: 10.1038/nature03066. Epub 2004 Oct 13.

Authors

David P Corey¹, 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, Duan-Sun Zhang

Affiliation

¹ Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. dcorey@hms.harvard.edu

PMID: 15483558
DOI: 10.1038/nature03066

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

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
Ion Channels / genetics
Ion Channels / immunology
Ion Channels / metabolism*
Mechanotransduction, Cellular / physiology*
Mice
Oligonucleotides / genetics
Oligonucleotides / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Rana catesbeiana
TRPA1 Cation Channel
Transient Receptor Potential Channels
Vertebrates / metabolism*
Zebrafish / metabolism
Zebrafish Proteins / biosynthesis
Zebrafish Proteins / genetics
Zebrafish Proteins / immunology
Zebrafish Proteins / metabolism*

Substances

Antibodies
Ion Channels
Oligonucleotides
RNA, Messenger
RNA, Small Interfering
TRPA1 Cation Channel
Transient Receptor Potential Channels
Trpa1 protein, mouse
Zebrafish Proteins
trpa1a protein, zebrafish