The overall aim of this project is to analyze the membrane properties of several isolated cell types from the inner ear using the whole cell voltage clamp technique. The cell types (outer hair cells [OHCs], Type II spiral ganglion cells, and Deiter cells) were chosen because they all functionally relate (directly or indirectly to the OHC system. This system has recently been shown to be very important for normal cochlear function. Several properties of OHCs will be studied, including their inward Ca+2 currents, the mechanism of gadolinium induced block of voltage induced OHC motility, and the frequency response of OHC motility. These evaluations will be made by measuring the voltage dependence of these currents and motility blocking effects, by comparing the motility characteristics to those of stretch receptors, and by measuring OHC mechanical response magnitude induced by AC stimuli. The ionic conductances of Type II spiral ganglion cells and Deiter cells will be analyzed to determine their roles in the OHC system. Specifically, Deiter cells, which are coupled to other supporting cells via gap junctions, will be evaluated via voltage clamp to determine whether they possess mechanisms (e.g., inwardly directed K+ currents) which might aid in the ionic homeostasis of the organ of Corti. Type II spiral ganglion cells will be evaluated in similar fashion to determine whether they possess the ionic conductances necessary for the transfer of acoustic information to the central nervous system. Since no electrophysiological information is available on this cell type, this is an important issue. Understanding these phenomena will shed light upon the role that OHCs play in fine frequency tuning within the organ of Corti via mechanical feedback mechanisms. They will also help elucidate the effects of pathologies of the outer hair cell system, including ionic imbalances (e.g., Meniere's disease), noise induced 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 #
5R01DC000273-10
Application #
3216384
Study Section
Hearing Research Study Section (HAR)
Project Start
1984-02-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
10
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
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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