3-D Reconstruction of the Cardiac Sarcoplasmic Reticulum Reveals a Continuous Network Linking T-Tubules: This Organization is Perturbed in Heart Failure
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: To unravel inter-species differences and commonalities between the relationship of the SR and t-t networks within cardiac myocytes, and the modifications that occur in heart failure employing a novel high resolution 3-D imaging technique.
Methods and Results: Employing serial block face imaging coupled with scanning electron microscopy and image analysis we have generated 3-D 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. 3-D 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 3-D 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 inter-species differences in E-C coupling and we report the first detailed analysis of SR remodeling as a result of heart failure.
- serial block face scanning electron microscopy
- sarcoplasmic reticulum
- excitation-contraction coupling
- heart failure
- Received March 11, 2013.
- Revision received September 17, 2013.
- Accepted September 17, 2013.