The organ of Corti is composed of a variety of cell types including sensory, supporting and neural elements. Taken together, these cells comprise a functionally intricate and cohesive electrical unit that initiates the analysis of acoustic information within our environment. This electrical unit is extremely complex and nearly anatomically inaccessible, making an analysis of the whole quite a challenge. Fortunately, during the last several years the in vitro approach, including the isolated cochlea and cell preparations, has aided in the elucidation of cell function; the strategy is to understand the cells first on an individual basis, and finally to integrate this knowledge into a complete understanding of the organ of Corti. The overall aim of this project is to analyze the membrane properties of the outer hair cell (OHC), one of the major players in auditory function, principally using variations on the whole cell voltage clamp technique. Three areas of investigation are proposed. Specifically, we intend to 1) analyze the mobility OHC sensor/motors in the lateral plasma membrane, 2) study in detail and make modifications to the electrical correlate of OHC motility, its nonlinear capacitance and analyze what such modifications will do to the high frequency mechanical activity of the OHC, and 3) study the mechanical coupling among OHCs that we have just discovered. These results will lead to a deeper understanding of inner ear function and aid in understanding auditory pathologies which may result from OHC insult and homeostatic imbalance, including sensorineural hearing loss and tinnitus.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
3R01DC000273-21S1
Application #
6788670
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Donahue, Amy
Project Start
1984-02-01
Project End
2005-03-31
Budget Start
2003-08-15
Budget End
2004-03-31
Support Year
21
Fiscal Year
2003
Total Cost
$50,000
Indirect Cost
Name
Yale University
Department
Surgery
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Santos-Sacchi, Joseph; Tan, Winston (2018) The Frequency Response of Outer Hair Cell Voltage-Dependent Motility Is Limited by Kinetics of Prestin. J Neurosci 38:5495-5506
Tan, Winston J T; Song, Lei; Graham, Morven et al. (2017) Novel Role of the Mitochondrial Protein Fus1 in Protection from Premature Hearing Loss via Regulation of Oxidative Stress and Nutrient and Energy Sensing Pathways in the Inner Ear. Antioxid Redox Signal 27:489-509
Song, Lei; Santos-Sacchi, Joseph (2016) A Walkthrough of Nonlinear Capacitance Measurement of Outer Hair Cells. Methods Mol Biol 1427:501-12
Santos-Sacchi, Joseph; Song, Lei (2016) Chloride Anions Regulate Kinetics but Not Voltage-Sensor Qmax of the Solute Carrier SLC26a5. Biophys J 110:2551-2561
McKay, Sharen E; Yan, Wayne; Nouws, Jessica et al. (2015) Auditory Pathology in a Transgenic mtTFB1 Mouse Model of Mitochondrial Deafness. Am J Pathol 185:3132-40
Santos-Sacchi, Joseph; Song, Lei (2014) Chloride-driven electromechanical phase lags at acoustic frequencies are generated by SLC26a5, the outer hair cell motor protein. Biophys J 107:126-33
Santos-Sacchi, Joseph; Song, Lei (2014) Chloride and salicylate influence prestin-dependent specific membrane capacitance: support for the area motor model. J Biol Chem 289:10823-30
Ricci, Anthony J; Bai, Jun-Ping; Song, Lei et al. (2013) Patch-clamp recordings from lateral line neuromast hair cells of the living zebrafish. J Neurosci 33:3131-4
Song, Lei; Santos-Sacchi, Joseph (2013) Disparities in voltage-sensor charge and electromotility imply slow chloride-driven state transitions in the solute carrier SLC26a5. Proc Natl Acad Sci U S A 110:3883-8
Okunade, Oluwarotimi; Santos-Sacchi, Joseph (2013) IR laser-induced perturbations of the voltage-dependent solute carrier protein SLC26a5. Biophys J 105:1822-8

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