TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells.
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.
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. dcorey@hms.harvard.edu
David P
DP
Corey
Jaime
J
García-Añoveros
Jeffrey R
JR
Holt
Kelvin Y
KY
Kwan
Shuh-Yow
SY
Lin
Melissa A
MA
Vollrath
Andrea
A
Amalfitano
Eunice L-M
EL
Cheung
Bruce H
BH
Derfler
Anne
A
Duggan
Gwénaëlle S G
GS
Géléoc
Paul A
PA
Gray
Matthew P
MP
Hoffman
Heidi L
HL
Rehm
Daniel
D
Tamasauskas
Duan-Sun
DS
Zhang
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000276:immunology; D007758:Ear, Inner / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000378:metabolism*; D006309:Hearing / Q000502:physiology*; D017403:In Situ Hybridization; D007473:Ion Channels / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011892:Rana catesbeiana; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; D014714:Vertebrates / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D007473:Ion Channels; D009841:Oligonucleotides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D029961:Zebrafish Proteins; C494579:trpa1a protein, zebrafish