Membrane properties of cells comprising the OHC system

构成 OHC 系统的细胞的膜特性

• 批准号: 7157225
• 负责人: JOSEPH R SANTOS-SACCHI
• 金额: $ 4.51万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157225
• 关键词: cell membrane; cell motility; cochlea; ear hair cell; ear pharmacology; efferent nerve; electrostimulus; ganglion cell; guinea pigs; intercellular connection; membrane activity; membrane potentials; neurotransmitters; organ of Corti; salicylate; second messengers; temperature; voltage /patch clamp; voltage gated channel

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 clamp technique. Three areas of investigation are proposed. Specifically, we intend to 1) study in detail the mechanical sensitivity of the OHC lateral membrane as it relates to chloride flux, 2) study the effects of chloride and anions on the OHC motor activity, and 3) study mechanical coupling among OHCs in an explant organ of Corti preparation. The results that we will obtain will lead to a deeper understanding of inner ear function and aid in understanding auditory pathologies, which may result from OHC insult and homeostatic imbalance, including sensorineural hearing loss and tinnitus.

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。这个电气单元非常复杂，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钳技术的变化。提出了三个调查领域。具体而言，我们打算1）详细研究OHC侧膜的机械敏感性，因为它与氯离子通量有关，2）研究氯离子和阴离子对OHC运动活性的影响，3）研究Corti制备的外植体器官中OHC之间的机械耦合。我们将获得的结果将导致对内耳功能的更深入了解，并有助于理解可能由OHC损伤和稳态失衡引起的听觉病理，包括感音神经性听力损失和耳鸣。