ACTIVATION OF CA++ RELEASE IN SKELETAL AND HEART MUSCLE

骨骼肌和心肌中 CA 释放的激活

• 批准号: 2750454
• 负责人: JOHN L SUTKO
• 金额: $ 21.76万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2750454
• 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

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+ 释放家族 渠道。 许多脊椎动物共表达两种 RyR 同工型 骨骼肌和这些肌肉中 SR Ca2+ 的释放似乎利用 两种异构体。 我们不知道两个 RyR 系统如何运作以及目标 该项目的目的是确定该系统的属性以及它如何 有助于激活肌肉收缩。 此外，我们 将比较这些肌肉中的 Ca2+ 释放与心肌中的 Ca2+ 释放 其中似乎表达了单个 RyR 同工型。 我们将测试 假设两个 RyR 串联运作，每个亚型是 专门用于通过与任一相互作用激活 二氢吡啶受体 (DHPR) 或 Ca2+。 我们将使用骨骼肌 制剂：单独表达每种 RyR 同工型或两种 RyR 同工型 组合，并利用 CaO 依赖性或 Ca 非依赖性 SR Ca2+ 释放机制。 在项目的第一阶段，我们将定义 每个 RyR 如何被激活以及 Ca2+ 的功能特性 与每次准备相关的电流和 SR Ca2+ 释放瞬变。 在这项工作的第二阶段，我们将研究 Ca2+ 的作用 发布系统组织确定所使用的发布过程。 将使用光和电子显微技术来建立 细胞结构和与每个 RyR 和相关的非 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 每种异构体介导的 Ca2+ 释放事件。 的相关性 这些研究的结果将使我们能够定义功能 双 RyR Ca2+ 释放系统的特性、影响因素和条件 确定所使用的发布系统以及发布者所做的贡献 不同的Ca2+释放系统对胚胎肌肉发育和成熟的影响 肌肉功能。