MECHANOELECTRICAL TRANSDUCTION IN ADULT OUTER HAIR CELLS

描述(申请人提供)：外毛细胞(OHC)是Corti器官中的两个受体细胞之一，在哺乳动物的听力中起着关键作用。内耳毛细胞通过耳蜗内的局部机械反馈过程来增强基底膜的运动，被称为耳蜗放大器，一般认为耳蜗体长变化是内耳毛细胞的电压依赖性体长变化的基础。在该方案中，传感器电流响应于声刺激而产生的感受器电位为细胞的运动活动提供输入。因此，OHC被认为具有两种转导功能，即在立体纤毛中执行常规的机电或正向转导，以及在基底外侧膜上执行特殊的机电或反向转导。尽管低等脊椎动物和哺乳动物前庭毛细胞中的机械电转导已被很好地研究，但主要由于技术上的困难，在成年耳蜗毛细胞中的前向转导过程基本上还没有被探索。因此，目前还不清楚传感器电流有多大，也不清楚电流是否也具有低等脊椎动物毛细胞中的适应能力。此外，由于基底膜的直接运动，还没有人尝试测量换能器电流。这项探索性/发展性研究的目标是在更接近活体且相对完整的半绒毛标本中同时记录OHC换能器电流和基底膜运动。具体地说，将测量作为基底膜运动的换能器电流和膜电位。此外，还将确定成年OHC的换能器电流是否具有适应性。半角沙土鼠将从25至30天龄的沙鼠身上准备。全细胞膜片钳技术将被用来记录由振动的玻璃纤维引起的基底膜运动过程中来自内脏细胞的换能器电流和膜电位。用光电子学技术测量基膜的运动。同时记录换能器电流和基底膜运动是研究毛囊细胞转导过程的重要一步。由于大多数美国听力损失患者(总计约3000万人)存在某种毛细胞损伤，了解毛细胞的运作对于毛细胞相关的听力损失和耳聋的生物修复和预防至关重要。

DESCRIPTION (provided by applicant): The outer hair cell (OHC) is one of two receptor cells in the organ of Corti, and plays a critical role in mammalian hearing. OHCs enhance basilar membrane motion through a local mechanical feedback process within the cochlea, termed the 'cochlear amplifier', it is generally believed that the basis of cochlear amplification is a voltage-dependent somatic length change of OHCs. In this scheme, receptor potentials produced by transducer current in response to acoustic stimulation provide the input to the cell's motor activity. Consequently, the OHC is thought to perform two transducer functions, a conventional mechanoelectrical or forward transduction in the stereocilia and a specialized electromechanical or reverse transduction in the basolateral membrane, Although the mechanoelectrical transduction in low-vertebrate and mammalian vestibular hair cells has been well studied, the forward transduction process in adult cochlear hair ceils has essentially not been explored, primarily because of technical difficulties. Therefore, it is still unclear how large the transducer current is and whether the current also has adaptation like that seen in low-vertebrate hair cells. Furthermore, no attempt has ever been made to measure transducer currents as a result of direct basilar membrane motion. The goal of this Exploratory/Developmental Research is to record OHC transducer current and basilar membrane motion simultaneously in a more in vivo-like and relatively intact preparation, the hemicochlea. Specifically, the transducer currents and membrane potentials as a function of basilar membrane motion wilt be measured. Whether the transducer current of adult OHCs has adaptation will also be determined. Hemicochlea will be prepared from 25- to 30-day-old gerbils. Whole cell patch-clamp techniques will be used to record transducer currents and membrane potentials from OHCs during basilar membrane motion evoked by a vibrating glass fiber. The motion of the basic membrane will be measured by optoelectronical technique. Simultaneous recording of the transducer current and basilar membrane motion is a significant step forward in studying the transduction process in OHCs. Because the majority of Americans with hearing loss, some 30 million in all, have some kind of hair cell damage, understanding the operation of OHCs is essential to the biological remediation and prevention of hair cell-related hearing loss and deafness.