CALCIUM REGULATION OF MYOCARDIAL CONTRACTION

这笔赠款的目的是向首席调查员提供 稳定的长期工资支持，使她能够进一步发展她的研究 职业生涯。提供这种支持将使申请人能够 大大减轻了她的行政和服务负担，并集中精力 在这里描述的实验程序上。短期目标(在 支持期)是为了阐明钙结合在 横纹肌的收缩。长期目标包括加强 候选人作为独立调查员在以下领域的地位 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。该中心为 生物工程为人类提供了强有力的研究和教育环境 实现这些目标和所需的最先进的设备 该项目已经到位，并完全发挥了作用。内部协作 和中心之外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来 为了研究哺乳动物骨骼肌和心肌的几个方面 钙在激活和收缩中的作用。电子探头 微量分析将被用来测量在交界处隔离的钙 大鼠和雪貂乳头肌的肌浆网部位 在各种情况下，长期目标是 了解细胞内和细胞外钙在心脏中的相对作用 伸缩性。骨骼和心脏皮肤纤维的相关实验 将讨论结合在肌丝上的钙的作用。电子探头 将用于测量A、I和I的交叉桥状态和肌节长度 重叠区域。使用数字化结构分析蒙皮和 使用冷冻骨折深蚀刻复制品的完整肌肉样本将解决 肌球蛋白细丝的结构变化是否 与钙结合和激活有关。由于许多内生性和 临床使用的药物被认为通过改变心输出量来改变心输出量 钙，这些结果可能对理解 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.