CELLULAR BASIS OF TUNING IN THE COCHLEA

耳蜗调节的细胞基础

• 批准号: 2733698
• 负责人: JONATHAN JAMES ART
• 金额: $ 22.37万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733698
• 关键词: Chelonia; calcium flux; cochlear nerve; confocal scanning microscopy; ear hair cell; efferent nerve; electrostimulus; neural plasticity; potassium channel; sound frequency; voltage /patch clamp; voltage gated channel

The goal of the proposed research is to characterize the cellular mechanisms that contribute to tuning in the cochlea. Using a combination of patch electrode and fluorescence imaging techniques on both solitary hair cells and in intact basilar papillae from the red-eared turtle. Trachemys scripta elegans, we will address two questions: (1) how does the expression of channels that determine the characteristic frequency vary along the length of the epithelium; and (2) how is the quality of resonance modulated by efferent fibers and mechanical properties of the hair cell? In answering the first question we will test the hypothesis that tuning in lower frequency cells is due to an ensemble of voltage-dependent potassium conductances: a partially-adapting outwardly-rectifying conductance (KV), and an inwardly-rectifying conductance (KIR). Furthermore, by precisely correlating channel expression and characteristic frequency in the intact epithelium, we will test in situ the prediction that the major currents, ICa and IK(Ca), previously implicated in tuning higher frequency hair cells at the base of the epithelium are supplemented or replaced by IKV and IK(IR) at the apex. Additional experiments will test the plasticity of channel expression by acclimating turtles to different body temperatures over a range of 20oC. The experiments addressing the second question test the hypothesis that the quality of hair cell resonance is modulated not only by the activity of efferent fibers, but by mechanical properties of the hair cell as well. Voltage-clamp experiments on hair cells in the intact epithelium will be used to dissect the ionic basis of post synaptic potentials produced by electrical stimulation of efferent fibers. We will also explore the hypothesis that the mechanism of efferent activity is mediated not only via modulation of two basolateral hair cell conductances, buy may also include a component from apical synapses near the transduction pole. Included are experiments that explore whether the voltage-dependent bundle motion of turtle hair cells is detected by transduction channels and thereby modulates the quality of electrical resonance. The final experiments will use confocal microscopy to examine the role of Ca2minus as a common intracellular effector for both efferent and mechanical input. By understanding how these cellular mechanisms determine frequency selectivity, we will be able to assess their limitations and applicability to the physiology and pathophysiology of hearing in higher vertebrates, including man.

这项拟议研究的目标是描述细胞的特性 有助于耳蜗调谐的机制。使用 贴片电极与荧光成像技术的结合 红耳鱼的单个毛细胞和完整的基底乳头 乌龟。Trachemys Scripta elegans，我们将解决两个问题：(1) 决定特征的通道的表达如何 频率随上皮的长度而变化；以及(2)如何 传出光纤和机械调制的共振质量 毛细胞的特性？ 在回答第一个问题时，我们将测试调谐 在较低频率的单元中是由于电压依赖的集合 钾电导：一种部分适应的外向整流 电导(KV)和向内整流电导(KIR)。 此外，通过精确地将通道表达和 在完整的上皮中，我们将在原位测试 预测先前涉及的主要洋流ICa和Ik(Ca) 在调谐上皮基底部的高频毛细胞时 在顶端用IKV和IK(IR)补充或取代。其他内容 实验将通过驯化来测试通道表达的可塑性 在20摄氏度的范围内，海龟可以适应不同的体温。 解决第二个问题的实验验证了这样的假设 毛细胞共振的质量不仅受活动的调节 但也取决于毛细胞的机械性能。 对完整上皮中的毛细胞进行电压钳实验 用来剖析由人产生的突触后电位的离子基础 电刺激传出纤维。我们还将探索 假设传出活动的机制不仅是中介的 通过调节两个基底侧毛细胞电导，Buy也可能 包括转导极点附近顶端突触的成分。 其中包括探索电压依赖关系的实验 通过转导通道检测甲鱼毛细胞的束状运动 并由此调节电共振的质量。决赛 实验将使用共聚焦显微镜来检查Ca2minus的作用 作为一种共同的细胞内传出和机械效应器 输入。 通过了解这些细胞机制如何决定频率 选择性，我们将能够评估它们的局限性和适用性 对于高等脊椎动物听力的生理学和病理生理学， 包括人类。