CELLULAR BASIS OF TUNING IN THE COCHLEA

耳蜗调节的细胞基础

• 批准号: 6379400
• 负责人: JONATHAN JAMES ART
• 金额: $ 24.44万
• 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 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379400
• 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.

拟议研究的目的是表征细胞 有助于在耳蜗中调整的机制。 使用 斑块电极和荧光成像技术的组合 孤立毛细胞和完整的基底乳头 龟。 Trachemys Scripta Exemans，我们将解决两个问题：（1） 如何决定特征的通道的表达 频率随上皮的长度而变化； （2）如何 共振的质量由传出纤维和机械调节 毛细胞的特性？ 在回答第一个问题时，我们将测试调整的假设 在较低的频率细胞中，是由于电压依赖性的合奏 钾电导：部分适应外向 电导（KV）和内向矫正的电导（KIR）。 此外，通过精确相关的通道表达和 完整上皮的特征频率，我们将原位测试 预测主要电流ICA和IK（CA），以前暗示 在调整上皮底部的较高频率毛细胞时 在顶点的IKV和IK（IR）补充或取代。 额外的 实验将通过适应来测试通道表达的可塑性 在20oC的范围内，海龟到不同的体温。 解决第二个问题的实验测试了一个假设 毛细胞共振的质量不仅受活动调节 传出纤维，但也通过毛孔的机械性能。 完整上皮的毛细胞的电压钳实验将是 用于剖析由 电刺激纤维的电刺激。 我们还将探索 假设传出活性的机制不仅是介导的 通过调节两个基底外侧毛孔电导，购买也可能 包括来自转导极附近的顶端突触的成分。 包括探索电压依赖性的实验 通过转导通道检测到乌龟毛细胞的束运动 从而调节电共振的质量。 决赛 实验将使用共聚焦显微镜检查CA2Minus的作用 作为传出和机械的常见细胞内效应子 输入。 通过了解这些细胞机制如何确定频率 选择性，我们将能够评估他们的局限性和适用性 对于高脊椎动物的听力的生理学和病理生理学， 包括男人。