FIGURE 3.

Dilatation of t-tubules in disease and ageing. (A) Dilated sheet-like tubules (red) were observed in x-y (upper) and x-z view (lower) by Seidel et al. (2017) in ventricular tissues of patients with chronic heart failure. (B) Magnified views illustrate how a subset of RyR clusters (green) appeared to align with these sheet-like tubules (red). (C) Similar sheet-like tubules were observed by us in confocal micrographs of ventricular muscle tissue from a human patient with end-stage idiopathic dilated cardiomyopathy (IDCM). (D) Magnified view illustrates how a majority of local RyR clusters (grey) are re-arranged along the sheet-like tubules (extending longitudinally, shown in red) instead of maintaining the sarcomeric pattern (transverse). (E,F) Compared, are dSTORM images from transverse tissue sections of ventricular cells of young adult (9-weeks old) and aged (100 weeks) stained for t-tubule marker Caveolin-3, respectively. Whilst local dilatations or pockets were observed in the t-tubules in both age groups (arrowheads), macro-tubules (typically > 300 nm in diameter; asterisk in D) were observable. (G,H-i) Super resolution of both normal and IDCM t-tubules revealed Collagen-VI (red) encased within the tubule lumina whilst dystrophin (green) lined the tubules (magnified view shown in G,H-ii). (G,H-iii) Illustrate how the limited resolution in the equivalent confocal data fail to reveal this spatial feature in non-dilated t-tubules (in the non failing myocardium). Scale bars: (A): 10 μm, (B): 2 μm, (C): 15 μm, (D): 2 μm, (E,F): 2 μm. (G-i,Hi): 1 μm, (G-ii,iii,H-ii,iii): 250 nm. (A,B) Adapted from Seidel et al. (2017) with permission; (E,F) from Crossman et al. (2017) with permission.