ACTIVATION OF CA++ RELEASE IN SKELETAL AND HEART MUSCLE

骨骼肌和心肌中 CA 释放的激活

基本信息

批准号：
6043837
负责人：
JOHN L SUTKO
金额：
$ 22.62万
依托单位：
UNIVERSITY OF NEVADA RENO
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-08-01 至 2002-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6043837
关键词：
age difference calcium channel calcium flux chick embryo histogenesis immunologic assay /test laboratory rabbit myocardium protein isoforms protein structure function receptor expression striated muscles

项目摘要

Ryanodine receptors (RyR) form a family of intracellular Ca2+ release channels. There is co-expression of two RyR isoforms in many vertebrate skeletal muscles and SR Ca2+ release in these muscles appears to utilize both isoforms. We do not know how a two-RyR system operates and the goal of this project is to establish the properties of this system and how it contributes to the activation of muscle contraction. In addition, we will compare Ca2+ release in these muscles with that in cardiac muscle where a single RyR isoform appears to be expressed. We will test the hypothesis that the two RyRs operate in series with each isoform being specialized for activation by interactions with either the dihydropyridine receptor (DHPR) or Ca2+. We will use skeletal muscle preparations: that express each RyR isoform singly or both RyR isoforms in combination, and that utilize CaO-dependent or Ca -independent SR Ca2+ release mechanisms. In the first phase of the project, we will define how each RyR can be activated and the functional properties of the Ca2+ currents and SR Ca2+ release transients associated with each preparation. In the second phase of this work we will investigate the role of Ca2+ release system organization in determining the release process used. Light and electron microscopic techniques will be used to establish the cellular structures and the nonRyR proteins associated with each RyR and each SR Ca2+ release mechanism. In the final phase of this project, we will establish the cellular conditions responsible for the maturation of the Ca2+ release transient. In addition, we will define the properties of the Ca2+ release events mediated by each isoform. Correlations of the results from these studies will permit us to define the functional properties of a two-RyR Ca2+ release system, factors and conditions that determine the release system used, and the contributions made by the different Ca2+ release systems to embryonic muscle development and mature muscle function.

Ryanodine受体（RYR）形成细胞内Ca2+释放的家族频道。许多脊椎动物中有两个RYR同工型的共表达这些肌肉中的骨骼肌和SR Ca2+释放似乎都在使用两种同工型。我们不知道两种ryr系统的运行方式和目标这个项目的是建立该系统的属性以及如何建立有助于肌肉收缩的激活。另外，我们将比较这些肌肉中的Ca2+释放与心肌中的释放其中似乎表达单个RYR同工型。我们将测试假设两个RYR串联起作用，每种同工型为专门用于通过与任何一个二氢吡啶受体（DHPR）或Ca2+。我们将使用骨骼肌肉准备工作：单独表达每个RYR同工型或两个RYR同工型结合使用，并利用CAO依赖或与CA独立的SR Ca2+ 释放机制。在项目的第一阶段，我们将定义如何激活每个RYR以及Ca2+的功能特性电流和SR Ca2+释放瞬变与每次制剂相关。在这项工作的第二阶段，我们将研究Ca2+的作用释放系统组织在确定所使用的发布过程中。光和电子微观技术将用于建立细胞结构和与每个RYR相关的非Ryr蛋白每个SR CA2+释放机制。在这个项目的最后阶段，我们将建立负责成熟的细胞条件 Ca2+释放瞬态。此外，我们将定义属性由每个同工型介导的Ca2+释放事件。相关性这些研究的结果将使我们能够定义功能两ryr Ca2+释放系统的特性，因素和条件确定所使用的发布系统，以及不同的Ca2+释放系统，用于胚胎肌肉发育和成熟肌肉功能。