Electromechanics of the Cochlear Outer Hair Cell

外毛细胞（OHC）是正常哺乳动物听力所必需的。它们将电力转换为机械 能量和有助于耳蜗放大器，放大和改善内耳中的声音振动。 干扰它们的机电力产生机制会导致听力损失。机制 负责产生这种力的细胞位于OHC的质膜上。所有的膜似乎都能 将电力转化为机械力。OHC膜含有一种称为普雷斯廷的蛋白质， 过程此外，圆柱形OHC在吸收膜产生的力方面是有效的， 使其平行于它们的纵轴。这是通过一个优雅的，三层，复合 这种纳米结构在生物学上是独一无二的，就像它在听觉中所起的作用一样。该提案的一个目标是 了解普雷斯廷和外侧壁的纳米级机械解剖结构如何促进OHC 机电力的产生，特别是在声频。普雷斯廷的作用是由 检查它的存在或不存在如何改变机电转换。药物的作用和 已知细胞内氯离子浓度的变化可改变OHC中的机电转导 并由此调节听力。协调实验， 数学和计算方法将决定侧壁的组织如何引导 由质膜产生的机电力。OHC的三个具体目标 机械性能和机电转换在逐步扩大规模开始与 细胞膜和终止于整个细胞。电压钳和光镊配合使用， 三个具体目标。具体目标1检查质膜中的机电转导， 研究膜系链对跨膜电位变化的机械响应。 这些实验将确定单独膜的机电转换系数。 具体目标2探测侧壁的反应，具体目标3检查力学和 整个细胞的电子力学。最终的结果将是一个完整的描述OHC机电 力的产生及其在听觉中的作用。

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.