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

骨骼肌激活（兴奋-收缩偶联）涉及信号 通过专门的膜连接（三联体）， 横小管（T系统）与肌浆网。 目的 这项研究的目的是描述一个非线性的潜在变化， 发生在T系统膜上，大概是在三联体连接处。 这 一种现象最近被私家侦探发现。使用电位染料， 被证明反映了瞬时静电势的变化， 在去极化后，与兴奋收缩密切相关 偶合器. 这项研究将研究这种现象与 Q γ运动，现在认为这反映了一种构象变化， T细胞系统中的电压敏感分子，介导连接 传输 此外，它将检查的生理功能 这种现象及其与分子机制的关系 结耦合 这些问题将通过详细比较 非线性静电势变化，电荷移动。 的 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 它允许同时测量T系统光信号和电荷 运动 这项研究可以更好地了解正常的机制， 肌肉激活 此外，它是广泛相关的肌肉萎缩症 涉及兴奋-收缩偶联异常， 设计治疗剂，例如肌肉松弛剂丹曲林钠+， 特别是改变这个过程。

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.