Comparison of the organization of t‐tubules, sarcoplasmic reticulum and ryanodine receptors in rat and human ventricular myocardium

Summary 1. It is apparent from the literature that there are significant differences in excitation–contraction coupling between species, particularly in the density of calcium transporting proteins in the t-system and sarcoplasmic reticulum (SR) Ca2+ release channels. Unfortunately, there is a lack of information as to how the principal structures that link electrical excitation to the activation of calcium-induced calcium release (CICR) are different between human and animal models (particularly rat). 2. Comparison of wheat germ agglutinin and caveolin-3 labelling revealed a non-uniform distribution of surface membrane glycosylation in the rat, rabbit and human, and that the rat t-system appeared more complex in geometry than the latter species. Analysis of the t-system skeleton showed that the t-system was highly branched in the rat compared with that of the human (0.8 ± 0.08 and 0.2 ± 0.07 branch points per μm2, respectively; P < 0.001). 3. We also compared the distribution of contractile machinery, sodium–calcium exchange, SR and ryanodine receptors (RyR) in rat and human. F-Actin and RyR labelling was used to estimate the area of contractile apparatus supplied by each RyR cluster. In the rat, each RyR cluster supplied an average cross-sectional area of contractile machinery of 0.36 ± 0.03μm2 compared with 0.49 ± 0.04 μm2 in human (P = 0.048). Sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a) labelling showed that the SR formed a tight network of loops surrounding contractile fibrils that were denser than the t-tubule network, but otherwise appeared similar in both species. 4. In general, the results show a higher density in structures involved in CICR in the rat compared with human.