title: Three-dimensional reconstruction of cardiac sarcoplasmic reticulum reveals a continuous network linking transverse-tubules: this organization is perturbed in heart failure.
abstract: BACKGROUND
  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.
  
  
  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 Ca(2+) 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.
authors.affiliation: From the Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, United Kingdom.
authors.forename: Christian
authors.initials: C
authors.lastname: Pinali
authors.forename: Hayley
authors.initials: H
authors.lastname: Bennett
authors.forename: J Bernard
authors.initials: JB
authors.lastname: Davenport
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Trafford
authors.forename: Ashraf
authors.initials: A
authors.lastname: Kitmitto
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D056966:Excitation Contraction Coupling / Q000502:physiology; D006333:Heart Failure / Q000473:pathology* / Q000503:physiopathology; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008297:Male; D008855:Microscopy, Electron, Scanning; D008929:Mitochondria, Heart / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000502:physiology / Q000648:ultrastructure*; D012756:Sheep; D013045:Species Specificity
keywords: 3D imaging; electron microscopy; excitation contraction coupling; heart failure; mitochondria; sarcoplasmic reticulum; t-tubules