MESOSCALE MODELING OF CARDIAC CALCIUM-INDUCED CALCIUM-RELEASE

心脏钙诱导钙释放的介观建模

• 批准号: 7957635
• 负责人: RAIMOND Lester WINSLOW
• 金额: $ 2.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957635
• 关键词: Anatomic structures; Calcium; Cardiac; Cardiac Myocytes; Computer Retrieval of Information on Scientific Projects Database; Data; Electrons; Experimental Models; Funding; Grant; Image; Image Analysis; Inositol; Institution; Ion Channel; Location; Maps; Microscopic; Mitochondria; Modeling; Na(+)-K(+)-Exchanging ATPase; Organelles; Property; Research; Research Personnel; Resources; Role; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Sarcoplasmic Reticulum; Signal Transduction; Source; Structure; Techniques; United States National Institutes of Health; base; nanometer; receptor; research study; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this collaborative project is to undertake a combined experimental and modeling study investigating how calcium (Ca2+) signaling, in what we refer to as the Ca2+-release microdomain (CCRM), influences properties of calcium-induced calcium-release (CICR) in the cardiac myocyte. We loosely define the CCRM as consisting of the cardiac ¿¿dyad,¿¿ adjacent anatomic structures (e.g., transverse tubules: T-tubules, and junctional sarcoplasmic reticulum: jSR), and organelles (e.g., mitochondria), which are sufficiently close to the dyad (within several hundred nanometers) that they may influence local CICR. We will use tools and techniques optimized to achieve three-dimensional (3D) tomographic electron microscopic (EM) imaging of CCRM structures, including mapping of the locations of ion channels and exchangers, such as L-type Ca2+ channels (LCCs), type 2 ryanodine receptors (RyR2s), the Na+-Ca2+ exchanger (NCX1), the Na+-K+ ATPase (NKA), and type 2 inositol 1,4,5-trisphosphate receptors (InsP3Rs). We will utilize these structural data to develop an experiment-based structurally and biophysically detailed model of cardiac CCRM. The model will be used to investigate the role of CCRM structure and channel placement on CICR.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 中心，不一定是研究者的机构。 该合作项目的目标是进行一项实验和建模相结合的研究，研究钙 (Ca2+) 信号（我们称之为 Ca2+ 释放微域 (CCRM)）如何影响钙诱导钙释放 (CICR) 的特性我们粗略地将 CCRM 定义为由心脏 ¿ ¿二元组, ¿ ¿邻近的解剖结构（例如，横管：T 管和交界肌浆网：jSR）和细胞器（例如，线粒体），它们距离二元体足够近（在几百纳米内），可能会影响局部 CICR。将使用优化的工具和技术来实现 CCRM 结构的三维 (3D) 断层电子显微镜 (EM) 成像，包括离子位置的映射通道和交换器，例如 L 型 Ca2+ 通道 (LCC)、2 型兰尼碱受体 (RyR2s)、Na+-Ca2+ 交换器 (NCX1)、Na+-K+ ATP 酶 (NKA) 和 2 型肌醇 1,4,5 -三磷酸受体（InsP3Rs）。我们将利用这些结构数据来开发基于实验的心脏结构和生物物理详细模型。 CCRM。该模型将用于研究 CCRM 结构和渠道布局对 CICR 的作用。