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 language | English (US) |
|---|---|
| Pages (from-to) | 723-730 |
| Number of pages | 8 |
| Journal | Nature |
| Volume | 432 |
| Issue number | 7018 |
| DOIs | |
| State | Published - Dec 9 2004 |
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TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. / Corey, David P.; Garcia-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.
In: Nature, Vol. 432, No. 7018, 09.12.2004, p. 723-730.Research output: Contribution to journal › Article
TY - JOUR
T1 - TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells
AU - Corey, David P.
AU - Garcia-Añoveros, Jaime
AU - Holt, Jeffrey R.
AU - Kwan, Kelvin Y.
AU - Lin, Shuh Yow
AU - Vollrath, Melissa A.
AU - Amalfitano, Andrea
AU - Cheung, Eunice L M
AU - Derfler, Bruce H.
AU - Duggan, Anne
AU - Géléoc, Gwénaëlle S G
AU - Gray, Paul A.
AU - Hoffman, Matthew P.
AU - Rehm, Heidi L.
AU - Tamasauskas, Daniel
AU - Zhang, Duan Sun
PY - 2004/12/9
Y1 - 2004/12/9
N2 - 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.
AB - 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.
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U2 - 10.1038/nature03066
DO - 10.1038/nature03066
M3 - Article
VL - 432
SP - 723
EP - 730
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7018
ER -