MOLECULAR MECHANISM OF OUTER HAIR CELL ELECTROMOTILITY

点击翻译按钮获取中文摘要

The long-term goal of this research is to develop an understanding of the mechanism of outer hair cell (OHC) electromotility and its control by the central nervous system. OHCs are capable of dynamic length changes at high speeds in response to potential differences across their membranes. Movement of membrane-bound charged particles connected to a highly developed cortical cytoskeleton may underlie OHC electromotility. Hypothetical molecular motors, having one or more charges, may couple voltage differences across the cell membrane to the cells mechanical motion. One specific aim of this project is to determine the number of motors (and their associated charges) which exist in each OHC based on quantitative models of their behavior and properties. Olivocochlear bundle efferents release acetylcholine (ACh) onto OHCs. ACh has been shown to increase OHC electromotility. The second specific aim of this project is to determine whether the effect of ACh is via the molecular motors or via a stiffness change. OHC whole-cell voltage clamp methods will be used to measure OHC charge movement (nonlinear capacitance) in control cells, deflated cells and in cells exposed to different ACh concentrations. Pharmacological treatment of the cells may provide clues as to which second messenger cascade is activated by ACh to produce its effects. The results of these studies contribute to our understanding of OHC mechanics and their contribution to normal mammalian hearing. This information may be clinically relevant for physicians treating patients with tinnitus or who are hard of hearing.