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

Abstract

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±0.04μm2 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. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.