MOLECULAR MECHANISM OF OUTER HAIR CELL ELECTROMOTILITY

这项研究的长期目标是了解 外毛细胞（OHC）电活动的机制及其受 中枢神经系统OHC能够动态改变长度， 它们对跨膜电位差的反应速度更快。 膜结合的带电粒子的运动连接到一个高度 发达的皮层细胞骨架可能是OHC电活动的基础。 假设的分子马达，有一个或多个电荷， 通过细胞膜到细胞机械的电压差 议案该项目的一个具体目标是确定 每个OHC中存在的电机（及其相关费用）， 它们的行为和性质的定量模型。橄榄耳蜗 束传出神经将乙酰胆碱（ACh）释放到OHC上。ACh已经 显示增加OHC电活动性。第二个具体目标是 项目是确定ACh的作用是否是通过分子 电机或通过刚度变化。OHC全细胞电压钳方法 将用于测量OHC电荷移动（非线性电容）， 对照细胞、放气细胞和暴露于不同ACh的细胞中 浓度的对这些细胞的药物治疗可能会提供线索 至于第二信使级联是由乙酰胆碱激活， 方面的影响.这些研究的结果有助于我们了解 OHC机制及其对正常哺乳动物听力的贡献。这 信息可能与治疗患者的医生临床相关 耳鸣或重听的人。

The long-term goal of this research is to develop an understanding of the mechanism of outer hair cell (OHC) electromotility and its control by the central nervous system. OHCs are capable of dynamic length changes at high speeds in response to potential differences across their membranes. Movement of membrane-bound charged particles connected to a highly developed cortical cytoskeleton may underlie OHC electromotility. Hypothetical molecular motors, having one or more charges, may couple voltage differences across the cell membrane to the cells mechanical motion. One specific aim of this project is to determine the number of motors (and their associated charges) which exist in each OHC based on quantitative models of their behavior and properties. Olivocochlear bundle efferents release acetylcholine (ACh) onto OHCs. ACh has been shown to increase OHC electromotility. The second specific aim of this project is to determine whether the effect of ACh is via the molecular motors or via a stiffness change. OHC whole-cell voltage clamp methods will be used to measure OHC charge movement (nonlinear capacitance) in control cells, deflated cells and in cells exposed to different ACh concentrations. Pharmacological treatment of the cells may provide clues as to which second messenger cascade is activated by ACh to produce its effects. The results of these studies contribute to our understanding of OHC mechanics and their contribution to normal mammalian hearing. This information may be clinically relevant for physicians treating patients with tinnitus or who are hard of hearing.