CALCIUM RELEASE UNITS IN CARDIAC MUSCLE

本项目的目标是了解 成人和发育中心肌的钙释放单位。这些单位 形成于肌浆网(SR)和表面的交界处 膜(及其内陷、横管、T管)。在这些地方 结，表面膜的电信号被换能器 从SR中释放出钙。两种膜分子：脚 (Ryanodine受体、SR钙释放通道)和慢钙 二氢吡啶受体(DHPR)参与释放 以及在分别启动它的事件中。第三个已确定 分子存在于连接处，即钙结合蛋白 钙固醇胺。本项目将探索这两者之间的关系 成年和发育心肌中的三个分子，使用 免疫组织化学和电子显微镜的两种方法：冰冻 骨折和选择性染色。在成人肌肉中，关键问题是 骨骼中存在的类型的特定空间关系 肌肉，存在于二氢吡啶受体和脚之间。我们希望 更好地理解 启动心肌活动，并确定哪些结构 是e-c耦合的显著差异的原因。 骨骼肌和心肌的特性。在肌肉发育过程中， 横管分化与血管内皮细胞分化的关系 将三种主要蛋白质组装成功能单位 下定决心。大部分关于开发的初始工作将被执行 关于鸡心，这里是发育程序，从最初的形成 功能收缩细胞的分化到完全 发达的肌肉纤维，是在时间上延伸的。来自禽类的信息 肌肉将与生理学最好的大鼠肌肉相关联 已经成立了。

The goal of this project is to understand the structure and assembly of calcium release units in adult and developing cardiac muscle. The units are formed at junctions between sarcoplasmic reticulum (SR) and surface membrane (and its invaginations, the transverse, T, tubules). At these junctions, the electrical signal of the surface membrane is transduced into a release of calcium from the SR. Two membrane molecules: feet (ryanodine receptors, SR calcium release channels) and slow calcium channels (dihydropyridine receptors, DHPRs) are involved int he release and in the events initiating it respectively. A third identified molecule is present at the junctions, the calcium binding protein calsequestrin. This project will explore the relationship between these three molecules in adult and developing cardiac muscle, using immunohistochemistry and two approaches to electron microscopy: freeze- fracture and selective staining. In adult muscle the key question is whether a specific spatial relationship, of the type present in skeletal muscle, exists between dihydropyridine receptors and feet. We hope to achieve a better understanding of the structures underlying the initiation of cardiac muscle activity, and to determine which structures are responsible for the significant differences in e-c coupling properties of skeletal and cardiac muscle. In developing muscle, the relationship between differentiation of transverse tubules, and the assembly of the three major proteins into functional units will be determined. Most of the initial work on development will be performed on chicken heart, where the developmental program, from initial formation of a functional contractile cell to the differentiation of a fully developed muscle fiber, is extended in time. Information from avian muscle will be correlated to rat muscle, whose physiology is best established.