Species differences in the morphology of T-tubule openings in cardiomyocytes

Aims: The ultrastructure of ventricular cardiomyocyte T-tubule connections with the outer cell surface has been reported to be different between mice and rabbits. In mice, T-tubules form convoluted narrow spaces filled with electron-dense matter that impedes diffusion between T-tubular lumen and bulk extracellular space. Here, we explore whether T-tubule mouths are also restricted in rat (another murine model used frequently for cardiac research) and whether pig and human T-tubule mouths are also generally restricted as is the case for mouse.

Methods: We used chemically-fixed tissue and high-pressure frozen cells to compare T-tubule mouth architecture in rats, mice, and rabbits using transmission electron microscopy and 3D electron tomography.

Results: We find that rat T-tubular mouth architecture is more similar to that of rabbits than mice, lacking the marked tortuosity and electron-dense ground substance that obstructs access to deeper portions of the T-tubular system in mice. Pilot observations in larger mammals (pig, human) suggest that mouse may be the least representative animal model of T-tubule connectivity with the outer cell surface in larger mammals.

Conclusion: Rat T-tubular system architecture appears to be more similar in size and topology to other mammals than mice. T-tubular mouth topology may contribute to differences in experimental model behaviour, underscoring the problems of appropriate model selection for research into cell and tissue functions.