Biophysics and Biomechanics of the Semicircular Canals

NIH RePORTER · NIH · R01 · $324,063 · view on reporter.nih.gov ↗

Abstract

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.

Key facts

NIH application ID
9933876
Project number
5R01DC006685-16
Recipient
UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
Principal Investigator
RICHARD D RABBITT
Activity code
R01
Funding institute
NIH
Fiscal year
2020
Award amount
$324,063
Award type
5
Project period
2004-05-01 → 2023-06-30