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 which initiates the analysis of acoustic information within our environment. The outer hair cell (OHC) is believed to be responsible for our enhanced ability to resolve acoustic information. During the last few years the in vitro approach 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 isolated cell types (spiral ganglion cells, supporting cells, and OHCs ) from the inner ear using the whole cell voltage clamp technique, and video analysis of the OHC mechanical response. Specifically, we intend to 1) study the ionic conductances of spiral ganglion cells, 2) study in detail and make modifications to the electrical correlate of OHC motility, its nonlinear capacitance, 3) analyze what such modifications will do to the high frequency mechanical activity of the OHC, 4) determine compartmentalization of the ionic conductances and motility voltage sensors within the membrane of the OHC, and 5) continue analyzing control mechanisms of cell coupling in supporting cells. 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.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Hearing Research Study Section (HAR)
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Yale University
Schools of Medicine
New Haven
United States
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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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