The outer hair cell (OHC) of the mammalian cochlea, a sensory receptor cell, generates force when electrically stimulated. OHC force, driven in vivo by the acoustic receptor potential, is thought to contribute an extra step of mechanical excitation (the """"""""cochlear amplifier"""""""") that improves tuning and is vulnerable to disease and insult. Recent experiments in this laboratory have shown that the axial stiffness of the OHC is essential to connect the OHC voltage-dependent motor to its load, the organ of Corti. But nothing is known about OHC stiffness at relevant acoustic frequencies nor are the cellular components underlying OHC stiffness understood. This proposal has three specific aims that will provide this information.
In Aim1, OHC impedance (stiffness) will be measured directly at acoustic frequencies using a novel instrument, the laser stretcher. Whether membrane potential modulates impedance-a proposed mechanism of the cochlear amplifier-will be tested. The first direct measurement of isometric force will be made.
In Aim 2, the role of OHC stiffness in the development of hearing will be determined, specifically whether the onset of OHC stiffness is a limiting event in development of the cochlear amplifer.
In Aim 3, the role of the cortex, a subcellular structure in OHC stiffness will be determined using a developmental approach.
| Hallworth, Richard; Nichols, Michael G (2012) Single molecule imaging approach to membrane protein stoichiometry. Microsc Microanal 18:771-80 |
| Vergen, Jorge; Hecht, Clifford; Zholudeva, Lyandysha V et al. (2012) Metabolic imaging using two-photon excited NADH intensity and fluorescence lifetime imaging. Microsc Microanal 18:761-70 |
| Jensen-Smith, Heather; Currall, Benjamin; Rossino, Danielle et al. (2009) Fluorescence microscopy methods in the study of protein structure and function. Methods Mol Biol 493:369-79 |
| Dossou, Starlette J Y; Bre, Marie-Helene; Hallworth, Richard (2007) Mammalian cilia function is independent of the polymeric state of tubulin glycylation. Cell Motil Cytoskeleton 64:847-55 |
| Tiede, Leann M; Rocha-Sanchez, Sonia M; Hallworth, Richard et al. (2007) Determination of hair cell metabolic state in isolated cochlear preparations by two-photon microscopy. J Biomed Opt 12:021004 |
| Jensen-Smith, Heather; Hallworth, Richard (2007) Lateral wall protein content mediates alterations in cochlear outer hair cell mechanics before and after hearing onset. Cell Motil Cytoskeleton 64:705-17 |
| Hallworth, Richard; Currall, Benjamin; Nichols, Michael G et al. (2006) Studying inner ear protein-protein interactions using FRET and FLIM. Brain Res 1091:122-31 |
| Vent, Julia; Wyatt, Todd A; Smith, D David et al. (2005) Direct involvement of the isotype-specific C-terminus of beta tubulin in ciliary beating. J Cell Sci 118:4333-41 |
| Jensen-Smith, Heather C; Eley, Jonquille; Steyger, Peter S et al. (2003) Cell type-specific reduction of beta tubulin isotypes synthesized in the developing gerbil organ of Corti. J Neurocytol 32:185-97 |
| Jensen-Smith, Heather C; Luduena, Richard F; Hallworth, Richard (2003) Requirement for the betaI and betaIV tubulin isotypes in mammalian cilia. Cell Motil Cytoskeleton 55:213-20 |
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