OPTICAL STUDIES OF T-SYSTEM FUNCTION IN E-C COUPLING

E-C 耦合中 T 系统功能的光学研究

• 批准号: 3160576
• 负责人: JUDITH A HEINY
• 金额: $ 6.6万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3160576
• 关键词: Anura; calcium channel blockers; conformation; dantrolene; electron density; muscle contraction; muscle relaxants; muscular dystrophy; myofibrils; neural information processing; neuromuscular transmission; receptor coupling; sarcoplasmic reticulum; striated muscles; voltage /patch clamp

Skeletal muscle activation (excitation-contraction coupling) involves signal transmission across specialized membrane junctions (triads) that join the transverse tubules (T-system) with the Sarcoplasmic Reticulum. The purpose of this research is to characterize a non-linear potential change that occurs in the T-system membranes, presumably at the triadic junctions. This phenomenon was recently discovered by the P.I. using potentiometric dyes and was shown to reflect a transient electrostatic potential change that occurs upon depolarization and is closely associated with excitation-contraction coupling. The research will examine the relationship of this phenomenon to Q gamma movement, which is now thought to reflect a conformational change on the voltage-sensing molecule in the T-system that mediates junctional transmission. Additionally, it will examine the physiological function of this phenomenon and its relationship to the molecular mechanism of junctional coupling. These questions will be addressed by making detailed comparisons of the non-linear electrostatic potential change, with charge movement. The measurements will be performed using single voltage-clamped muscle fibers stained with potentiometric dyes and mounted in an experimental apparatus that allows simultaneous measurement of T-system optical signals and charge movement. This research can lead to a better understanding of the mechanisms of normal muscle activation. Also, it is broadly relevant to muscular dystrophies that involve an abnormality of excitation-contraction coupling and to the design of therapeutic agents such as the muscle relaxant Dantrolene Na+ that specifically alter this process.

骨骼肌激活（激发反应耦合）涉及信号 加入的专用膜连接（三合会）的传输 带有肌质网的横向小管（T-System）。 目的 这项研究的特征是表征非线性潜在变化 发生在T-System膜中，大概是在三合会连接处。 这 现象最近被P.I.发现使用电位计量染料和 被证明反映了发生的瞬态静电电势变化 去极化后，与激发反应密切相关 耦合。 该研究将研究这种现象与 Q伽玛运动，现在被认为反映了对 介导连接的T系统中的电压传感分子 传播。 此外，它将检查 这种现象及其与分子机制的关系 连接耦合。 这些问题将通过对 通过电荷运动，非线性静电电势变化。 这 将使用单电压夹肌纤维进行测量 用电位计量染料染色并安装在实验设备中 这允许同时测量T系统光学信号和电荷 移动。 这项研究可以更好地理解正常机制 肌肉激活。 此外，它与肌肉营养不良广泛有关 这涉及激发反应耦合的异常 设计治疗剂，例如肌肉松弛剂Dantrolene Na+ 专门更改此过程。