Electromechanics of the Cochlear Outer Hair Cell

哺乳动物的正常听力需要外毛细胞(OHC)。他们把电气转换成机械 它可以提供能量，并有助于耳蜗放大器放大和优化内耳的声音振动。 干扰它们的机电作用力产生机制会导致听力损失。这一机制 负责这股力量的产生驻留在OHC的质膜中。所有的膜似乎都能 把电转化为机械力。OHC膜含有一种名为prestin的蛋白质，它能增强 这一过程。此外，圆柱形OHC有效地承受了薄膜产生的力和 使其平行于它们的纵轴。这是通过一个优雅的三层复合材料来实现的 在生物上独一无二的纳米结构，就像它在听力中所起的作用一样。这项提议的一个目标是 了解Prestin和侧壁的纳米级机械解剖如何促进OHC 机电作用力的产生，特别是在声频下。预设的作用由以下因素决定 研究它的存在或不存在如何改变机电转导。药物和药物的作用 细胞内氯离子浓度的变化可改变OHC的机电转导 并因此对所有实验操作的听力调制进行评估。协同实验， 数学和计算方法将决定侧墙的组织如何引导 质膜产生的机电作用力。调查OHC的三个具体目标 机械特性和机电转换在逐步更大的尺度上开始 细胞膜，并与整个细胞结束。电压钳和光镊子一起使用。 三个具体目标。特异靶1研究质膜中的机电转导 研究膜系绳对跨膜电位变化的机械响应。 这些实验将单独确定膜的机电转换系数。 特指2探测侧壁的响应和特指3检查力学和 整个电池的机电系统。最终的结果将是对OHC机电的完整描述 力的产生及其在听力中的作用。

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.