SUBSPECIALIZATION OF CARDIAC SARCOPLASMIC RETICULUM

假设心脏肌浆网（SR） 亚特化的 拟议研究的目标是记录这一点 一种体外生物化学方法。 一种异质性心脏SR制备方法 将离心分离成兰尼碱敏感（RS）亚群 和对鱼米碱不敏感（RI）的SR囊泡，以及不同的功能， SR的两个亚群的组成和形态特征 囊泡确定。功能研究将解决Ca 2+代谢。 初步数据表明RI囊泡具有高的Ca 2+泵， 密度和高的Ca 2+吸收能力。 RS的Ca 2+吸收 囊泡被药物ryanodine选择性地刺激，ryanodine可以阻断 不同的Ca 2+外排通道仅存在于这些囊泡中。 组成研究将表征两种蛋白质中的独特蛋白质 小泡的亚群负责它们不同的Ca 2 加上处理性能，形态学研究将确定 两种SR在完整内膜中的亚细胞定位。 虽然其他人已经分离出功能不同的SR亚群， 这项研究是第一次尝试从骨骼肌， 准备工作 本研究将进一步阐明SR在调节 哺乳动物心肌的兴奋-收缩偶联。

The hypothesis is that cardiac sarcoplasmic reticulum (SR) is subspecialized. The goal of the proposed research is to document this with an in vitro biochemical approach. A heterogeneous cardiac SR preparation will be centrifuged into subpopulations of ryanodine dine-sensitive (RS) and ryanodine-insensitive (RI) SR vesicles, and the different functional, compositional, and morphological properties of the two subpopulations of SR vesicles determined. Functional studies will address Ca2 plus metabolism. Preliminary data indicate that RI vesicles have a high Ca2 plus pump density and a high capacity for Ca2 plus uptake. Ca2 plus uptake by RS vesicles is selectively stimulated by the drug, ryanodine, which may block distinct Ca2 plus efflux channels present only in these vesicles. Compositional studies will characterize unique proteins in either subpopulation of vesicles which are responsible for their different Ca2 plus handling properties, and morphological studies will determine the subcellular localization of the two types o SR in intact meocardium. Although others have isolated functionally different subpopulations of SR from skeletal muscle, this study is the first to attempt this with cardiac preparations. This study will further clarify the role of SR in regulating excitation-contraction coupling in mammalian myocardium.