Architecture of the cardiac transverse–axial tubular system across different mammalian species

Abstract

Cardiac excitation–contraction coupling relies on a pancellular network of regular cardiomyocyte surface membrane invaginations, termed the transverse–axial tubular system (TATS). The TATS is ubiquitously present in adult mammalian cardiomyocytes, enabling efficient structural and functional coupling of sarcolemma and intracellular Ca ²⁺ stores. However TATS ultrastructural characteristics across species, and their relation to cardiomyocyte morphology and physiological parameters such as heart rate, remain largely unexplored. Here we quantified TATS and cardiomyocyte features in a confocal microscopy dataset (91 three‐dimensional image volumes) obtained from tissue slices across eight species (mouse, rat, rabbit, pig, horse, elephant, whale, and humans). We applied a semi‐automated image analysis pipeline to quantify mean cytosolic distances to the nearest TATS element (Cyto‐TATS _min ), transverse tubule fraction, and cardiomyocyte dimensions. Cyto‐TATS _min and transverse tubule fraction differed substantially between species, with the lowest Cyto‐TATS _min in mouse and highest in humans. No significant within‐species associations between Cyto‐TATS _min and cardiomyocyte size were detected in six of eight species. Associations were limited to pig (cross‐sectional area and width) and elephant (area, depth, and width), although elephant was represented by a single subject. Across all species, Cyto‐TATS _min positively correlated with species’ lifespan and body mass, and was inversely correlated with resting heart rate. Our findings reveal structural scaling principles in cardiac cellular ultrastructure and provide a resource for studying TATS organisation in health and disease. As TATS remodelling is a common hallmark of cardiac pathology, awareness of species differences in reference states and remodelling dynamics is needed to guide the design and interpretation of translational research. image