CALCIUM REGULATION OF MYOCARDIAL CONTRACTION

该补助金的目的是为主要研究者提供 稳定的长期工资支持，使她能够进一步发展她的研究 事业 这种支持的可用性将允许申请人 大大减轻行政和服务工作量， 在这里描述的实验项目上。 短期目标（ 支持期）的目的是阐明钙结合在 横纹肌收缩。 长期目标包括加强 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。 中心 生物工程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，并充分发挥作用。 内部合作 中心内外提供了一个极好的机会， 培训和富有成效的研究。 拟议的研究将采用分析和结构技术， 哺乳动物骨骼肌和心肌，以研究几个方面， 钙在激活和收缩中的作用。 电子探针 将使用微量分析来测量在连接处螯合的钙 大鼠和雪貂乳头肌中肌浆网的位置 在各种条件下，长期目标是 了解心肌细胞内和细胞外钙离子的相对作用， 收缩性 骨骼肌和心肌皮肤纤维的相关实验 将讨论钙与肌丝结合的作用。 电子探针 将用于测量A、I和B中的横桥状态和肌节长度， 重叠区域。 用数字结构分析的方法， 使用冷冻断裂深蚀刻复制品的完整肌肉样品将解决 肌球蛋白丝的结构变化是否 与钙结合和激活有关。 由于许多内源性和 临床上使用的药物被认为是通过改变 钙，这些结果可能是非常重要的了解， 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.