In this study, we described a novel t-tubule-dependent mechanism of cholinergic regulation of intracellular Ca2+ handling in ventricular myocytes that may be of importance in cardiac diseases, such as heart failure, which is associated with downregulated t-tubules (Brette and Orchard, 2003; Louch et al., 2010; Guo et al., 2013). Here, TBXT is linked to heart disorder.