CALCIUM REGULATION OF MYOCARDIAL CONTRACTION

这笔赠款的目的是为主要研究者提供 长期稳定的薪资支持，让她能够进一步发展自己的研究 职业生涯。 获得此类支持将使申请人能够 大大减少她的行政和服务负担并集中精力 关于本文描述的实验程序。 短期目标（期间 支持期）是为了澄清钙结合的作用 横纹肌收缩。 长期目标包括增强 候选人在以下领域作为独立调查员的地位 横纹肌调节和超微结构（特别强调 心肌）和计算机辅助图像分析。 该中心 生物工程为学生提供了强大的研究和教育环境 实现这些目标和所需的最先进的设备 该项目已到位且功能齐全。 内部合作 以及中心以外的地方提供了进一步发展的绝佳机会 培训和卓有成效的研究。 拟议的研究将应用分析和结构技术 哺乳动物的骨骼和心肌，以研究以下几个方面 钙在激活和收缩中的作用。 电子探针 微量分析将用于测量交界处螯合的钙 大鼠和雪貂乳头肌肌浆网的部位 在各种条件下，长期目标是 了解细胞内和细胞外钙在心脏中的相对作用 收缩性。 骨骼和心脏皮纤维的相关实验 将解决钙与肌丝结合的作用。 电子探针 将用于测量 A、I 和 中的横桥状态和肌节长度 重叠区域。 使用数字结构分析蒙皮和 使用冷冻断裂深蚀刻复制品的完整肌肉样本将解决 肌球蛋白丝的结构变化是否与肌球蛋白丝的结构变化有关？ 与钙结合和激活有关。 由于许多内源性和 临床使用的药物被认为可以通过改变心输出量来改变心输出量。 钙，这些结果对于理解钙的潜在非常重要 心脏的正常和病理功能。

The purpose of this grant is to provide the Principle Investigator with stable longterm salary support to allow her to further develop her research career. The availability of such support would permit the applicant to substantially reduce her administrative and service load and to concentrate on the experimental program described herein. Short-term goal (during the period of support) are to clarify the role of calcium binding at contraction in striated muscle. Long-term goals include enhancement of the candidate's standing as an independent investigator in the areas of striated muscle regulation and ultrastructure (with particular emphasis on cardiac muscle) and computer-aided image analysis. The Center for Bioengineering provides a strong research and educational environment for the attainment of these goals and the state-of-the-art equipment required for the project are in place and fully functional. Collaborations within and outside of the Center provide an excellent opportunity for further training and fruitful research. The proposed research will apply analytical and structural techniques to mammalian skeletal and cardiac muscle in order to study several aspects of the role of calcium in activation and contraction. Electron probe microanalysis will be used to measure calcium sequestered at junctional sites of the sarcoplasmic reticulum in rat and ferret papillary muscles under a variety of conditions, with the long-term objective being to understand the relative role of intra- and extracellular calcium in cardiac contractility. Related experiments on skeletal and cardiac skinned fibers will address the role of calcium bound to myofilaments. The electron probe will be used to measure crossbridge state and sarcomere length in A, I and overlap regions. The use of digital structural analysis of skinned and intact muscle samples using freeze fracture deep etch replicas will address the question of whether structural changes in the myosin filaments are associated with calcium binding and activation. Since many endogenous and clinically used agents are thought to modify cardiac output via changes in calcium, these results are potentially very important in understanding the normal and pathological functioning of the heart.