Three-Dimensional Reconstruction of Cardiac Sarcoplasmic Reticulum Reveals a Continuous Network Linking Transverse-Tubules This Organization Is Perturbed in Heart Failure
Three-Dimensional Reconstruction of Cardiac Sarcoplasmic Reticulum Reveals a Continuous Network Linking Transverse-Tubules This Organization Is Perturbed in Heart Failure
复制标题
DOI：
10.1161/circresaha.113.301348
复制
发表时间：
2013-11-08
影响因子：
20.1
通讯作者：
Kitmitto, Ashraf
中科院分区：
文献类型：
--
作者：
Pinali, Christian;Bennett, Hayley;Kitmitto, Ashraf
基本原理：横管状 (t-t) 系统的组织及其与肌浆网 (SR) 的关系支撑着心脏兴奋-收缩耦合。 SR 的结构以及与 t-ts 的关系在全细胞水平上尚未得到很好的表征。此外，对于心力衰竭中 SR 超微结构的变化知之甚少。 目的：本研究的目的是利用新型高分辨率 3 维 (3D) 成像技术，揭示心肌细胞内 SR 和 t-t 网络关系之间的种间差异和共性，以及心力衰竭中发生的改变。方法和结果：使用连续块面成像结合扫描电子显微镜和图像分析，我们对绵羊和心肌细胞的整个心肌细胞进行了 3D 重建。大鼠左心室，揭示了 SR 在两个物种的整个细胞中形成了一个连接 t-ts 的连续网络。在绵羊中，SR 与形成连接域的肌膜有着密切的关系，但在大鼠中则不然。 3D 重建还揭示了绵羊 t-t 系统的细节。使用快速起搏引起的心力衰竭模型，我们发现存在肿胀和塌陷的 t-t 群、SR 缠结斑块以及线粒体重排紊乱。结论：我们提供了 SR 网络的第一个高分辨率 3D 结构，表明它形成了一个全细胞范围的通信管道，促进 Ca2+ 扩散、缓冲和同步性。细胞内 SR 的分布与兴奋-收缩耦合的种间差异有关，我们报告了心力衰竭导致的 SR 重塑的首次详细分析。
Rationale: The organization of the transverse-tubular (t-t) system and relationship to the sarcoplasmic reticulum (SR) underpins cardiac excitation-contraction coupling. The architecture of the SR, and relationship with the t-ts, is not well characterized at the whole-cell level. Furthermore, little is known regarding changes to SR ultrastructure in heart failure.Objective: The aim of this study was to unravel interspecies differences and commonalities between the relationship of SR and t-t networks within cardiac myocytes, as well as the modifications that occur in heart failure, using a novel high-resolution 3-dimensional (3D) imaging technique.Methods and Results: Using serial block face imaging coupled with scanning electron microscopy and image analysis, we have generated 3D reconstructions of whole cardiomyocytes from sheep and rat left ventricle, revealing that the SR forms a continuous network linking t-ts throughout the cell in both species. In sheep, but not rat, the SR has an intimate relationship with the sarcolemma forming junctional domains. 3D reconstructions also reveal details of the sheep t-t system. Using a model of tachypacing-induced heart failure, we show that there are populations of swollen and collapsed t-ts, patches of SR tangling, and disorder with rearrangement of the mitochondria.Conclusions: We provide the first high-resolution 3D structure of the SR network showing that it forms a cell-wide communication pipeline facilitating Ca2+ diffusion, buffering, and synchronicity. The distribution of the SR within the cell is related to interspecies differences in excitation-contraction coupling, and we report the first detailed analysis of SR remodeling as a result of heart failure.