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: 3160579
• 负责人: JUDITH A HEINY
• 金额: $ 9.39万
• 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/3160579
• 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（兴奋-收缩耦合）涉及信号 跨特殊膜连接（三联体）的传输 横管（T 系统）与肌浆网。 目的 这项研究的目的是表征非线性潜在变化 发生在 T 系统膜中，大概是在三元连接处。 这 P.I.最近发现了这一现象。使用电位染料和 被证明可以反映发生的瞬态静电势变化 去极化时，与兴奋收缩密切相关 耦合。 该研究将探讨这一现象与 Q 伽玛运动，现在被认为反映了构象变化 T 系统中介导连接的电压感应分子 传播。 此外，还将检查生理功能 这种现象及其与分子机制的关系 连接耦合。 这些问题将通过详细比较来解决 非线性静电势变化，伴随电荷运动。 这 将使用单电压钳位肌纤维进行测量 用电位染料染色并安装在实验装置中 允许同时测量 T 系统光信号和电荷 移动。 这项研究可以使人们更好地了解正常的机制 肌肉激活。 此外，它与肌肉营养不良症广泛相关 涉及兴奋-收缩耦合异常和 治疗药物的设计，例如肌肉松弛剂 Dantrolene Na+ 特别改变这个过程。