Comparison of the organization of T-tubules, sarcoplasmic reticulum and ryanodine receptors in rat and human ventricular myocardium.

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) Ca(2+) 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 μm(2) , 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 ± 0.03μm(2) compared with 0.49 ± 0.04 μm(2) 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. Clinical and Experimental Pharmacology and Physiology