Fig. 1.

Disruption of t-tubule network in HF. In failing cardiomyocytes, there is progressive deterioration of t-tubule architecture, impeding the normal propagation of action potentials into the cardiomyocyte core. It has been proposed that “orphan” RyR2 are located outside the junctional cleft, triggering a second wave of CICR that perturbs synchronicity during systole and diastole. As these orphan RyR2 are located distant from the dyads, they are activated late, contributing to impaired contractile performance. Distorted t-tubule architecture may also impair signaling elicited by catecholamines and growth factors.