Quantifying the Role of Ca2+ in Mechanotransduction

量化 Ca2 在力传导中的作用

• 批准号: 7055470
• 负责人: HAMILTON E FARRIS
• 金额: $ 5.35万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-26 至 2006-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7055470
• 关键词: Chelonia; biological signal transduction; biomechanics; calcium; ear hair cell; electrophysiology; flash photolysis; fluorescence microscopy; hearing; neurophysiology; postdoctoral investigator; psychophysics; sound impedance; voltage /patch clamp

DESCRIPTION (provided by applicant): Mechanoelectric transduction (MET) in auditory hair cells employs multiple Ca2+ dependent processes that regulate activation, adaptation and the steady-state properties of the channel. These processes may be mediated either directly at the MET channel, as with Ca2+ block of the pore, or indirectly through accessory structures, such as myosin and its regulation of slow adaptation. Separately quantifying these processes is complicated by the fact that most are not only sensitive to both mechanical perturbation and Ca2+ but also exhibit interdependence: changes in the properties of one process elicit changes in another. For example, because adaptation is sensitive to stimulus rise time, alterations in activation kinetics are predicted to change adaptation. Thus, devising means to alter these processes independently is needed to better quantify their role in MET. The experiments are designed to circumvent these issues by using flash photolysis to regulate intracellular Ca2+ independently from mechanical stimulation. Understanding how Ca2+ regulates activation and adaptation has taken on more significance, as tonotopic variance in these processes suggests their kinetics are important in establishing a bandpass filter that may play a role in the tuning required for outer hair cell motility and the active process.

描述（由申请人提供）：听觉毛细胞中的机械电转导（MET）采用多个CA2+依赖性过程，这些过程调节了通道的激活，适应和稳态特性。这些过程可以直接在MET通道上介导，就像孔的Ca2+块一样，或通过辅助结构间接介导，例如肌球蛋白及其对缓慢适应的调节。通过大多数人不仅对机械扰动和Ca2+敏感，而且表现出相互依赖性：一个过程的性质的变化引起了另一个过程的变化，因此分别量化这些过程变得复杂。例如，由于适应对刺激的上升时间敏感，因此预计激活动力学的改变会改变适应性。因此，为了更好地量化其在MET中的作用，需要独立改变这些过程的方法。该实验旨在通过使用闪光光解来独立于机械刺激来调节细胞内Ca2+来避免这些问题。由于这些过程中的调整差异表明，了解CA2+如何调节激活和适应性的意义更大，这表明它们的动力学对于建立可能在外毛细胞运动所需的调整和活动过程中起作用的带通滤波器很重要。