MECHANISM OF OUTER HAIR CELL MOTILITY

外毛细胞运动机制

• 批准号: 3461941
• 负责人: RICHARD John HALLWORTH
• 金额: $ 4.77万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3461941
• 关键词: biomechanics; cell membrane; cell motility; chemical kinetics; ear hair cell; electrical conductance; electrical potential; electrophysiology; guinea pigs; mathematical model; potassium channel; single cell analysis; voltage gated channel

The long-term objective of these studies is to elucidate the mechanism of fast outer hair cell (OHC) motility. The results will be of central interest in basic studies of cochlear mechanism, because they will delineate the capabilities of OHC motility for energy input to the cochlea. This is a necessary precondition for serious theoretical and experimental examination of the role of OHC motility in cochlear function and pathology. An important secondary benefit of these studies is their contribution to cell biology about an extraordinarily fast motility mechanism, one that is unlike anything seen elsewhere to date. Five experimental studies are proposed. Three are designed to test concepts of the mechanism that have been derived from earlier studies and that have been formulated into a comprehensive mathematical model. In this model, motility is thought to be driven by a large number of independently-acting motor molecules located in the membrane of the cell's lateral wall. These "motors" are thought to change conformation in a stochastic voltage-dependent manner. One study will look for evidence of motor conformation changes in the noise statistics of the cell's average length. Another will examine the kinetics of motor activation at speeds not previously technically possible. The motor is believed to act antiphasically in the axial and radial directions. The third proposed study will examine the consistency of this action. A fourth study will determine the force generating capability of the OHC under load. Finally, in a fifth study, OHC motility will be used as an assay to determine the somatic location of voltage-dependent conductances. In addition, the model studies will be extended and new alternative model schemes examined. The model studies will proceed in parallel with and will complement the physiological studies.

这些研究的长期目标是阐明 快速外毛细胞（OHC）运动。 结果将是中央 对耳蜗机制的基础研究感兴趣，因为它们将 描述了OHC运动的能力，为能量输入到 耳蜗 这是严肃的理论和实践的必要前提。 耳蜗外毛细胞运动在耳蜗功能中作用的实验研究 和病理 这些研究的一个重要的次要好处是， 对细胞生物学的贡献， 机制，一个不同于任何其他地方看到的日期。 提出了五项实验研究。 三个是为了测试 从早期研究中得出的机制概念， 已经被公式化为一个全面的数学模型。 在 在这个模型中，运动性被认为是由大量的 独立作用的马达分子位于细胞膜上， 细胞的侧壁。 这些“马达”被认为可以改变 以随机电压依赖的方式。 一项研究将寻找 在噪音统计中的运动构象变化的证据， 细胞的平均长度 另一个将研究电动机的动力学 以以前技术上不可能的速度激活。 电机 据信在轴向和径向方向上反相地作用。 的 第三项拟议研究将审查这一行动的一致性。 一 第四项研究将确定作战中心的兵力生成能力 在负载下。 最后，在第五项研究中，OHC运动将被用作 用于确定电压依赖性的细胞定位的测定 电导率 此外，模型研究将得到扩展， 审查了替代模型方案。 模型研究将在 与生理学研究并行并将补充生理学研究。