Biophysics and Biomechanics of the Semicircular Canals

摘要目前的工作旨在推进角运动感觉的定量理解 通过半规管，特别注意嵴中的转导和信号传导的生物物理学 发束实验将使用一种新的转基因小鼠品系， 实验室成像毛束偏转和钙瞬变静纤毛，在某些情况下，通过 完整的壶腹而不破坏膜迷路。具体目标的动机是 初步数据定位刺激诱发的钙点几乎完全在高的tidal 静纤毛，数据表明随着刺激强度的增加，钙点向上移动。 增加，并且数据表明从转导位点到细胞体的超快钙信号传导。 具体目标1将使用生理学方法定位束中的机械-电转导通道。 刺激，检查随着刺激强度增加的通道募集，并绘制空间分布图。 转导在上皮表面的分布。特定目标2将测量轴向 刺激诱发静纤毛内钙点的运动，并检测其微机械电位 和化学动力学起源。特异性目标3将研究来自以下位点的超快钙信号传导： 在距离细胞体>40µm的毛束尖端进行转导。

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.