FUNCTION OF GIANT SARCOMERE MATRIX PROTEINS IN MUSCLE

肌肉中巨肌节基质蛋白的功能

• 批准号: 8361295
• 负责人: Henk L. GRANZIER
• 金额: $ 4.15万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361295
• 关键词: Biophysics; Cyclic AMP-Dependent Protein Kinases; Dextrans; Elements; Fiber; Funding; Grant; Head; Heart; Left; Length; Mechanics; Microfilaments; Mus; Muscle; Myosin ATPase; National Center for Research Resources; Pattern; Phosphorylation; Positioning Attribute; Principal Investigator; Protein Isoforms; Proteins; Relative (related person); Research; Research Infrastructure; Resources; Sarcomeres; Skin; Source; Starling (law); Thin Filament; United States National Institutes of Health; Ventricular; Work; X ray diffraction analysis; X-Ray Diffraction; base; connectin; cost; dextran; in vivo; mouse model; papillary muscle

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The increase in Ca2+ sensitivity that occurs when sarcomere length (SL) is increased (LDA), is considered the cellular basis of the Frank-Starling law of the heart. LDA is also influenced by the isoform of titin, a long elastic molecule responsible for much of the passive tension in working hearts, present in a particular muscle. Recent findings show increased LDA in a mouse model in which the N2B spring element of titin has been excised (N2B KO) (Lee et al., 2010). Here we investigated LDA in the presence of 3% Dextran (to restore in vivo lattice spacing in skinned muscles), the effect of PKA phosphorylation on LDA, and structural changes of myofilaments by using low-angle X-ray diffraction. Fiber bundles of skinned papillary muscle from left ventricular of N2B KO and WT mice were used. The passive tension, SLs and X-ray diffraction patterns were collected at various SLs from 1.95 to 2.3¿m. From X-ray diffraction patterns, myofilament lattice spacing (LS; d10) and the position of the myosin head relative to the thin filaments (intensity ratio; I11/I10) were obtained. We also performed mechanical studies to characterize Ca2+ sensitivity and LDA.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 当肌节长度 (SL) 增加 (LDA) 时，Ca2+ 敏感性增加，被认为是心脏 Frank-Starling 定律的细胞基础。 LDA 还受到肌联蛋白亚型的影响，肌联蛋白是一种长弹性分子，负责工作心脏中的大部分被动张力，存在于特定的肌肉中。最近的研究结果显示，在肌联蛋白的 N2B 弹簧元件被切除（N2B KO）的小鼠模型中，LDA 增加（Lee 等，2010）。在这里，我们通过使用低角度 X 射线衍射研究了 3% 右旋糖酐（以恢复去皮肌肉体内晶格间距）存在下的 LDA、PKA 磷酸化对 LDA 的影响以及肌丝的结构变化。 使用来自 N2B KO 和 WT 小鼠左心室的去皮乳头肌纤维束。被动张力、SL 和 X 射线衍射图案是在 1.95 至 2.3 µm 的不同 SL 处收集的。根据 X 射线衍射图，可以获得肌丝晶格间距（LS；d10）和肌球蛋白头相对于细丝的位置（强度比；I11/I10）。我们还进行了机械研究来表征 Ca2+ 敏感性和 LDA。