SITE AND NATURE OF HAIR-CELL TRANSDUCTION

毛细胞是内耳的感觉受体细胞。 他们 环境中的机械刺激，如声音，转化为电刺激， 触发神经纤维进入大脑的反应， 称为机械-电转换。 机电一体化的关键事件 转导被认为是机械敏感孔的打开 称为毛细胞膜上的传导通道。 的目的 项目是回答两个基本问题，机电 转导：1）转导是如何发生的，即， 转导通道的生物物理性质，以及2）在哪里 转导发生的位置，也就是说，通道位于细胞中的哪个位置。 为了确定通道的生物物理特性，我们将使用 新发展的电生理技术，全细胞电压 钳，记录牛蛙内耳的单个毛细胞。 这项技术将使我们能够测量流动的微小电流 当用探针刺激细胞时，通过转导通道。 从这些测量中，我们可以估算出电导等性质， 离子电流的单一转导通道的数量， 一个细胞中的通道 我们还可以直接测量 通道的性质受到耳毒性药物的应用的影响， 氨基糖苷类抗生素链霉素 为了定位细胞中的转导通道，我们将使用 生理学和形态学技术的新组合。 一是 将使用全细胞电压钳来引起少量的 不溶性化合物在转导通道中形成。 那么我们将 用X射线显微分析，电子显微镜 用于检测极少量材料的方法。 了解转导通道的位置及其生物物理特性 性质将被证明是重要的，无论是在理解的速度， 在正常耳朵的转导敏感性和理解如何 暴露于噪声和耳毒性药物影响转导。

Hair cells are the sensory receptor cells of the inner ear. They transduce mechanical stimuli in the environment, such as sound, into electrical responses that trigger the nerve fibers going to the brain, a process called mechano-electric transduction. The key event in mechano-electric transduction is thought to be the opening of mechanically-sensitive pores called transduction channels in the hair-cell membrane. The aim of this project is to answer two basic questions about mechano-electric transduction: 1) how does transduction occur, that is, what are the biophysical properties of the transduction channel, and 2) where does transduction occur, that is, where are the channels located in the cell. To determine the biophysical properties of the channel, we will use a newly-developed electrophysiological technique, the whole-cell voltage clamp, to record from single hair cells of the inner ear of the bullfrog. This technique will allow us to measure the minute currents that flow through the transduction channels when a cell is stimulated with a probe. From these measurements, we can estimate such properties as the conductance of a single transduction channel to ionic currents, and the number of channels in a cell. We can also measure directly how the transduction channel's properties are affected by applications of such ototoxic drugs as the aminoglycoside antibiotic, streptomycin. In order to locate the transduction channels in the cell, we will use a novel combination of physiological and morphological techniques. First, we will use the whole-cell voltage-clamp to cause a samll amount of an insoluble compound to form in the transduction channel. Then we will locate this compound using X-ray microanalysis, a electron-microscopic method for detecting extremely small quantities of material. Knowing the location of the transduction channels and their biophysical properties will prove important both in understanding the speed and sensitivity of transduction in normal ears and in understanding how exposure to noise and ototoxic drugs effects transduction.