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.

Optical fibers guide light between separate locations and enable new types of fluorescence imaging. Fiber-optic fluorescence imaging systems include portable handheld microscopes, flexible endoscopes well suited for imaging within hollow tissue cavities and microendoscopes that allow minimally invasive high-resolution imaging deep within tissue. A challenge in the creation of such devices is the design and integration of miniaturized optical and mechanical components. Until recently, fiber-based fluorescence imaging was mainly limited to epifluorescence and scanning confocal modalities. Two new classes of photonic crystal fiber facilitate ultrashort pulse delivery for fiber-optic two-photon fluorescence imaging. An upcoming generation of fluorescence imaging devices will be based on microfabricated device components.Fiber-optic fluorescence imaging has become increasingly versatile over the last decade as fiber-based devices have declined in size but gained in functionality. Three classes of applications in live animal and human subjects provide the primary motivations for innovation in fiber-optic imaging. First, basic research on biological and disease processes would benefit enormously from instrumentation that permits cellular imaging under conditions in which conventional light microscopy cannot be used. Many cell types reside within hollow tissue tracts or deep within solid organs that are inaccessible to optical imaging without devices that can reach such locations in a minimally invasive manner. Flexible fiber-optic devices also allow handheld imaging and imaging in freely moving animals 1 . Second, fiber devices might be implanted within live subjects for long-term imaging studies. This capability will not only benefit research on the cellular effects of aging, development or experience, but also will lead to new in vivo assays for testing of drugs and therapeutics. By allowing examination of cells concurrently with observation of disease symptoms and animal behavior, fiber-optic imaging will permit studies correlating cellular properties and disease outcome in individual subjects over time and could reduce the numbers of animals needed. A third set of applications concerns development of minimally invasive clinical diagnostics and surgical procedures 2 . Although much work remains, fiber-optic instrumentation has already broadened the applicability of in vivo fluorescence imaging.The seeds for development of fiber optic in vivo imaging were planted by early uses of fiberoptics and fluorescence for chemical sensing and spectroscopy, including classic work on detection of intracellular redox states [3][4][5] . Use of fiber optics for remote sensing and spectroscopy remains strong today 6 , and has expanded to include bioluminescence detection 7 . The recent proliferation of fluorescent probes has widened the set of potential uses © 2005 Nature Publishing Group Correspondence should be addressed to M.J.S (mschnitz@stanford.edu). COMPETING INTERESTS STATEMENTThe authors declare that they have no co...

The mechanically gated transduction channels of vertebrate hair cells tend to close in approximately 1 ms after their activation by hair bundle deflection. This fast adaptation is correlated with a quick negative movement of the bundle (a "twitch"), which can exert force and may mediate an active mechanical amplification of sound stimuli in hearing organs. We used an optical trap to deflect bullfrog hair bundles and to measure bundle movement while controlling Ca(2+) entry with a voltage clamp. The twitch elicited by repolarization of the cell varied with force applied to the bundle, going to zero where channels were all open or closed. The force dependence is quantitatively consistent with a model in which a Ca(2+)-bound channel requires approximately 3 pN more force to open, and rules out other models for the site of Ca(2+) action. In addition, we characterized a faster, voltage-dependent "flick", which requires intact tip links but not current through transduction channels.