CELLULAR BASIS OF TUNING IN THE COCHLEA

耳蜗调节的细胞基础

• 批准号: 6030206
• 负责人: JONATHAN JAMES ART
• 金额: $ 23.04万
• 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/6030206
• 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.

提出的研究的目的是表征细胞