CALCIUM ION CONTROL IN CARDIAC FUNCTION

这个项目的总体目标是发现和澄清细胞 钙离子稳态的机制及其与收缩控制的关系 心肌的张力和松弛。本局各部门的成员 生物化学、生理学和医学将结合他们的努力，使用 本研究主要采用分子和细胞生物学的研究方法。项目 (Inesi)将研究肌浆网(SR)ATPase，涉及 ATP利用钙离子转运的分子机制 Thapsigargin的特异性抑制，定点突变的影响 以及表达功能性ATPase的基因转移技术 在各种细胞和心肌中。项目(罗杰斯和莱德勒)将 SR-ATPase与Ryanodine受体功能互补的研究 在心肌细胞中的作用，以及在心肌细胞中的调节作用 磷酸化，使用生物化学、基因 转染法、单细胞电压钳和高分辨率共聚焦钙离子 成像。侯赛因项目将研究钙离子止血的适应性 以及对SR ATPase抑制剂如thapsigarin和di-ATPase的调节。 丁基对苯二酚。最终项目(WADE)将使用遗传方法 肌钙蛋白I亚型基因差异调控的研究 心脏发育和成熟，确定参与其中的不同元素 这一调节，并揭示肌钙蛋白I的功能后果 肌丝激活中钙离子依赖的基因切换。这个 四个项目将与计划的研究协作和 技术交流。此外，核心A将提供显微镜，细胞 为所有项目提供文化和重组DNA援助。核心B将 提供行政支持。

The general aim of this program is to discover and clarify cellular mechanisms of Ca2+ homeostasis, as they relate to control of contractile tension and relaxation in cardiac muscle. Members of the departments of Biochemistry, Physiology and Medicine will combine their efforts, using mostly methods of Molecular and Cell Biology for this research. Project (Inesi) will study the sarcoplasmic reticulum (SR) ATPase, with regards to the molecular mechanism of ATP utilization for Ca2+ transport, the highly specific inhibition by thapsigargin, the effects of site directed mutations and the technology of gene transfer for expression of functional ATPase in various cells and cardiac muscle. Project (Rogers and lederer) will study the complementary functions of SR ATPase and Ryanodine Receptor channel in cardiac myocytes, as well as the modulatory effects of phosphorylation, using an integrated strategy of biochemistry, gene transfection, single cell voltage clamp and high resolution confocal Ca2+ imaging. Project (Hussain) will study the adaptation of Ca2+ hemostasis and the regulation of SR ATPase inhibitors such as thapsigargin and di- butyl-hydroquinone. The final Project (Wade) will utilize genetic methods to study the differential regulation of Troponin I isoform genes during heart development and maturation, identify separate elements involved in this regulation, and uncover the functional consequences of troponin I gene switching on the Ca2+ dependence of myofilaments activation. The four projects will interact with planned research collaborations and technical exchange. In addition Core A will provide Microscopy, Cell Culture and Recombinant DNA assistance to all projects. Core B will provide administrative support.