{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:22:46Z","timestamp":1792160566030,"version":"4.4.0"},"reference-count":76,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Cardiac excitation\u2013contraction coupling relies on a pancellular network of regular cardiomyocyte surface membrane invaginations, termed the transverse\u2013axial tubular system (TATS). The TATS is ubiquitously present in adult mammalian cardiomyocytes, enabling efficient structural and functional coupling of sarcolemma and intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      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\u2010dimensional image volumes) obtained from tissue slices across eight species (mouse, rat, rabbit, pig, horse, elephant, whale, and humans). We applied a semi\u2010automated image analysis pipeline to quantify mean cytosolic distances to the nearest TATS element (Cyto\u2010TATS\n                      <jats:sub>min<\/jats:sub>\n                      ), transverse tubule fraction, and cardiomyocyte dimensions. Cyto\u2010TATS\n                      <jats:sub>min<\/jats:sub>\n                      and transverse tubule fraction differed substantially between species, with the lowest Cyto\u2010TATS\n                      <jats:sub>min<\/jats:sub>\n                      in mouse and highest in humans. No significant within\u2010species associations between Cyto\u2010TATS\n                      <jats:sub>min<\/jats:sub>\n                      and cardiomyocyte size were detected in six of eight species. Associations were limited to pig (cross\u2010sectional area and width) and elephant (area, depth, and width), although elephant was represented by a single subject. Across all species, Cyto\u2010TATS\n                      <jats:sub>min<\/jats:sub>\n                      positively correlated with species\u2019 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.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70796-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The transverse\u2013axial tubular system (TATS) is essential for efficient excitation\u2013contraction coupling in cardiomyocytes and, consequently, normal cardiac function. However systematic comparisons of TATS architecture across mammalian species remain limited.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We analysed 91 three\u2010dimensional (3D) image volumes, obtained using confocal microscopy, from eight mammalian species (mouse, rat, rabbit, pig, horse, humans, elephant, whale) using a unified image analysis pipeline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            We quantified mean cytosolic distance to the nearest TATS element (Cyto\u2010TATS\n                            <jats:sub>min<\/jats:sub>\n                            ), transverse tubule percentage, and 3D cardiomyocyte morphology.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Cyto\u2010TATS\n                            <jats:sub>min<\/jats:sub>\n                            and transverse tubule percentage showed species\u2010dependent patterns, with Cyto\u2010TATS\n                            <jats:sub>min<\/jats:sub>\n                            being lowest in mouse and highest in human. Across species, Cyto\u2010TATS\n                            <jats:sub>min<\/jats:sub>\n                            covaries with organismal physiology (lifespan, body mass, and resting heart rate).\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our quantitative data provide a cross\u2010species reference framework for interpreting physiological adaptations and pathological remodelling of the cardiac TATS.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp291136","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:16:43Z","timestamp":1790317003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Architecture of the cardiac transverse\u2013axial 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