Membrane properties of cells comprising the OHC system

描述（由申请人提供）：Corti器官由多种细胞类型组成，包括感觉、支持和神经元件。总之，这些细胞组成了一个功能复杂和有凝聚力的电单元，启动了对我们环境中声学信息的分析。这个电气单元极其复杂，几乎无法解剖，因此对整个单元进行分析是一个相当大的挑战。幸运的是，在过去的几年里，体外方法，包括分离的耳蜗和细胞制备，有助于阐明细胞功能;策略是首先在个体的基础上理解细胞，最后将这些知识整合到对Corti器官的完整理解中。该项目的总体目标是分析外毛细胞（OHC）的膜特性，外毛细胞是听觉功能的主要参与者之一，主要使用全细胞电压和电流钳技术的变化。我们打算1）研究可能影响其运动性能的OHC膜的特征，2）研究OHC运动的氯依赖性变构调节和3）研究运动的生物物理敏感性的发育变化。我相信，这三个具体的研究目标的及时评估将有助于我们欣赏周边听觉系统性能的关键因素。 公共卫生相关性：随着普雷斯廷作为外毛细胞（OHC）的难以捉摸的侧膜运动蛋白的鉴定，我们面临着了解这种单一分子如何影响哺乳动物精致的听觉的可能性。为此，我们把我们的兴趣集中在确定如何变构调制的电机可能会引起电机的已知的生物物理属性，以及如何电机在发展过程中成熟。我们假设，了解这些分子活动将有助于理解OHC如何使我们能够听到这么好，反过来我们如何对抗OHC的病理，折磨数百万人。

DESCRIPTION (provided by applicant): The organ of Corti is composed of a variety of cell types including sensory, supporting and neural elements. Taken together, these cells comprise a functionally intricate and cohesive electrical unit that initiates the analysis of acoustic information within our environment. This electrical unit is extremely complex and nearly anatomically inaccessible, making an analysis of the whole quite a challenge. Fortunately, during the last several years the in vitro approach, including the isolated cochlea and cell preparations, has aided in the elucidation of cell function; the strategy is to understand the cells first on an individual basis, and finally to integrate this knowledge into a complete understanding of the organ of Corti. The overall aim of this project is to analyze the membrane properties of the outer hair cell (OHC), one of the major players in auditory function, principally using variations on the whole cell voltage and current clamp technique. We intend to 1) study characteristics of the OHC membrane that may impact on its motor performance, 2) study the chloride dependent allosteric modulation of the OHC motor and 3) study the developmental changes in the motor's biophysical sensitivities. I believe that the timely evaluation of these three specific research aims will help us appreciate key elements contributing to peripheral auditory system performance. PUBLIC HEALTH RELEVANCE: With the identification of prestin as the elusive lateral membrane motor protein of the outer hair cell (OHC), we are faced with the possibility of understanding how this single molecule can affect the mammal's exquisite sense of hearing. To that end, we have focused our interest on determining how allosteric modulation of the motor may give rise to the motor's known biophysical attributes, and how the motor matures during development. We hypothesize that understanding these molecular activities will aid in understanding how the OHC enables us to hear so well and in turn how we might combat pathologies of the OHC that afflict millions.