Physiology and patho-physiology of the cardiac transverse tubular system: Transverse (t)-tubules in the heart

Cardiac transverse (t)-tubules play a vital role in ensuring synchronous contraction. They contain L-type Ca2+ channels which closely couple with intracellular Ca2+ release channels throughout the cell to mediate a rapid and uniform Ca2+ release. The complexity of the t-tubule network varies between species and across cardiac chambers and is also highly labile with density increasing during development and decreasing in disease. Recent work using super-resolution and 3D electron microscopy has shown that t-tubules themselves are highly diverse structures with the proteins located on and around them differentially modulated compared to other sites within the cell. This review will summarise our current understanding of the t-tubule network in health and disease with focus on t-tubule heterogeneity, the importance of t-tubules in excitation-contraction coupling and the proteins responsible for t-tubule regulation.