FUNCTION OF GIANT SARCOMERE MATRIX PROTEINS IN MUSCLE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 当肌节长度（SL）增加（LDA）时发生的Ca 2+敏感性增加被认为是心脏的Frank-Starling定律的细胞基础。LDA还受到肌联蛋白同种型的影响，肌联蛋白是一种长的弹性分子，负责工作心脏中的大部分被动张力，存在于特定的肌肉中。最近的发现显示在其中肌联蛋白的N2 B弹簧元件已被切除（N2 B KO）的小鼠模型中LDA增加（Lee等人，2010年）。在这里，我们研究了LDA中存在的3%葡聚糖（恢复在体内晶格间距在皮肤肌肉），PKA磷酸化对LDA的影响，和肌丝的结构变化，通过使用低角X-射线衍射。 使用N2 B KO和WT小鼠左心室的去皮乳头肌纤维束。在1.95至2.3 μ m的各种SL下收集被动张力、SL和X射线衍射图。从X射线衍射图，肌丝晶格间距（LS; d10）和位置的肌球蛋白头相对于细丝（强度比; I11/I10），得到。我们还进行了机械研究，以表征Ca 2+敏感性和LDA。

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.