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.

正常的哺乳动物听力需要外毛细胞（OHC）。他们将电气转换为机械 能量并有助于耳蜗放大器，该放大器放大并完善了内耳的声音振动。 干扰其机电力产生机制会导致听力丧失。机制 负责这种力量产生的是OHC的质膜。所有膜似乎都能 将电气转换为机械力。 OHC膜中包含一种称为Prestin的蛋白质 过程。此外，圆柱形OHC可有效地吸收膜产生的力和 平行于其纵轴。这是通过优雅的三层复合材料来实现的 纳米结构在生物学上与听力一样独特。该提议的目标之一是 了解Prestin和纳米级的机械解剖结构如何促进OHC 机电力的产生，特别是在声学频率下。普雷斯汀的作用取决于 检查其存在或不存在如何改变机电转导。药物和 已知会改变OHC中机电转导的细胞内氯化物浓度的变化 因此，评估了所有实验操作的调节听力。协调的实验， 数学和计算方法将决定侧壁的组织如何指导 质膜产生的机电力。三个特定目标调查OHC 机械性能和逐渐较大尺度的电学转导从 细胞膜并以整个细胞结束。电压钳和光学镊子一起使用 三个具体目标。特定目标1通过 调查膜系对跨膜电位变化的机械响应。 这些实验将确定单独的膜机电转导系数。 具体目标2探测侧壁的响应和特定目标3检查了机械师和 整个细胞的机电学。最终结果将是OHC机电的完整描述 力量生产及其在听力中的作用。