Electromechanics of the Cochlear Outer Hair Cell

耳蜗外毛细胞的机电学

• 批准号: 7323305
• 负责人: WILLIAM E BROWNELL
• 金额: $ 49.53万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7323305
• 关键词: Accounting; Acoustics; Amplifiers; Anatomy; Anions; Caliber; Cell Communication; Cell membrane; Cell model; Cells; Cellular Membrane; Chloride Ion; Chlorides; Chlorpromazine; Cholesterol; Cochlea; Computer Simulation; Data; Dependence; Dimensions; Electric Stimulation; Elements; Embryo; Frequencies; Generations; Goals; Hair Cells; Hearing; Human; Individual; Knock-out; Knowledge; Labyrinth; Lateral; Liquid substance; Mammals; Measures; Mechanics; Membrane; Membrane Potentials; Membrane Proteins; Microscopy; Microspheres; Modeling; Monitor; Nanostructures; Organ of Corti; Outer Hair Cells; Pharmaceutical Preparations; Physiological; Play; Positioning Attribute; Process; Production; Property; Proteins; Protocols documentation; Radial; Range; Receptor Cell; Research Personnel; Role; Simulate; Source; Techniques; Testing; Viscosity; Work; base; electric field; electrical potential; electrical property; hearing impairment; in vivo; instrumentation; kidney cell; laser tweezer; mathematical model; nano; nanoscale; programs; rat Pres protein; research study; response; salicylate; sound; tectorial membrane; vibration; voltage; voltage clamp

Outer hair cells (OHC) are required for normal mammalian hearing. They convert electrical to mechanical energy and contribute to the cochlear amplifier that magnifies and refines sound vibrations in the inner ear. Interfering with their electromechanical force generating mechanism results in hearing loss. The mechanism responsible for this force production resides in the OHC's plasma membrane. All membranes appear able to convert electrical into mechanical force. The OHC membrane contains a protein called prestin thatenhances the process. In addition, the cylindrical OHCs are effective at taking the membrane generated force and directing it parallel to their longitudinal axis. This is achieved by an elegant, three layered, composite nanostructure that is as biologically unique as the role it plays in hearing. One goal of this proposal is to understand how prestin and the nanoscale mechanical anatomy of the lateral wall facilitate OHC electromechanical force production, particularly at acoustic frequencies. The role of prestin is determined by examining how its presence or absence alters electromechanical transduction. The effect of drugs and changes in the intracellular chloride concentration known to alter electromechanical transduction in the OHC and thereby modulate hearing are assessed for all experimental manipulations. Coordinated experimental, mathematical and computational approaches will determine how the organization of the lateral wall directs the electromechanical force generated by the plasma membrane. Three specific aims investigate OHC mechanical properties and electromechancial transduction at progressively larger scales beginning with the cell membrane and ending with the whole cell. Voltage-clamp and optical tweezers are used together in all three specific aims. Specific Aim 1 examines electromechanical transduction in the plasma membrane by investigating the mechanical response of membrane tethers to changes in the transmembrane potential. These experiments will determine the electromechanical transduction coefficient for the membrane alone. Specific Aim 2 probes the response of the lateral wall and Specific Aim 3 examines the mechanics and electromechanics of the whole cell. The final result will be a complete description of OHC electromechanical force production and its role in hearing.

外毛细胞（OHC）是正常哺乳动物听力所必需的。他们把电转化为机械