Biophysics and Biomechanics of the Semicircular Canals

半规管的生物物理学和生物力学

基本信息

批准号：
10164750
负责人：
RICHARD D RABBITT
金额：
$ 32.41万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-05-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10164750
关键词：
Actins Address Apical Attention Auditory Biomechanics Biophysical Process Biophysics Buffers Calcium Calcium Signaling Cell membrane Cells Data Dependence Disease Electrophysiology (science)Epithelial Equilibrium Esthesia Face Fistula Fluorescence Funding Goals Hair Hair Cells Homeostasis Image Impairment Individual Ion Channel Laboratories Length Location Maps Mathematics Measures Membrane Motion Mouse Strains Movement Pattern Pharmacology Physical condensation Physiological Play Proteins Quality of life Regulation Reporter Reporting Research Resolution Semicircular canal structure Sensory Sensory Hair Signal Transduction Site Spatial Distribution Stereocilium Stimulus Stretching Surface Techniques Tissues Transgenic Mice Type I Hair Cell Vision Work cellular imaging chemical kinetics electric field experimental study membranous labyrinth neuronal cell body recruit sample fixation transmission process two-photon voltage voltage clamp

项目摘要

Summary. The present work seeks to advance quantitative understanding of angular motion sensation by the semicircular canals, with specific attention to biophysics of transduction and signaling in crista hair bundles. Experiments will be done using a new transgenic mouse strain developed in our laboratory to image hair bundle deflection and calcium transients in stereocilia, in some cases through the intact ampulla without disrupting the membranous labyrinth. The specific aims are motivated by preliminary data localizing stimulus-evoked calcium puncta almost exclusively at the tipse of tall stereocilia, data demonstrating upward movement of calcium puncta as the stimulus strength is increased, and data suggesting ultrafast calcium signaling from the transduction site to the cell body. Specific Aim 1 will localize mechano-electrical transduction channels in the bundle using physiological stimulation, examine recruitment of channels as the stimulus strength is increased, and map the spatial distribution of transduction across the surface of the epithelium. Specific Aim 2 will measure axial movements of stimulus evoked calcium puncta in stereocilia, and examine potential micromechanical and chemical-kinetic origins. Specific Aim 3 will investigate ultrafast calcium signaling from the site of transduction at tips of hair bundles over a distance >40µm to the cell body.

概括。目前的工作旨在提高对角运动感觉的定量理解通过半圆形管，特别注意Crista中翻译和信号的生物物理学发束。实验将使用我们在我们的在某些情况下通过完整的截肢而不会破坏膜的迷宫。具体目标是由初步的数据将刺激诱发的钙点定位于谈话的尖端几乎完全 Stereocilia，数据表明钙点的向上运动是刺激强度的向上移动增加了，数据表明从翻译部位到细胞体的超快钙信号传导。特定的目标1将使用生理学将机械电气转导通道定位在束中刺激，随着刺激强度的提高，检查通道的募集，并绘制空间翻译在上皮表面的分布。特定目标2将测量轴向刺激的运动诱发了立体胶质的钙点，并检查潜在的微力机械和化学运动起源。特定目标3将研究从该地点的超快钙信号传导在远距离的头发束的尖端上转导至40µm，可与细胞体> 40µm。