The contraction of cardiomyocytes is regulated by electrical signals propagated by an exquisite system of membrane invaginations termed transverse (t)-tubules. This system ensures maximal and synchronous contraction. Loss of this system in heart failure is thought to be a key mechanism impairing cellular contractility. Artificial loss of the t-tubules induced by de-tubulating agents results in profound impairments of contractility.Clinical studies have shown the ability, in selected patients, of mechanical unloading using left ventricular assist device therapy to induce regression of pathological remodeling in heart failure. So called reverse remodeling has been described at many levels.I will discuss the hypothesis that the t-tubule system is regulated by mechanical loading conditions in a dynamic and time-dependent manner.