Disordered yet functional atrial t-tubules on recovery from heart failure

Transverse (T)-tubules are vital for the synchronous rise of systolic calcium. Heart failure (HF) is commonly associated with t-tubule loss leading to dyssynchronous calcium release. Recovery from HF is associated with t-tubule restoration and
normalisation of systolic calcium. The mechanisms that control t-tubules remain unknown, thus we aim to determine; i) if atrial t-tubule loss in HF can be recovered, ii) the effect of t-tubule restoration on systolic calcium, iii) proteins involved in t-tubule recovery.

HF was induced in sheep by rapid ventricular pacing. Rapid pacing lead to loss of virtually all atrial t-tubules and the initial rise of calcium was restricted to the surface sarcolemma. Cessation of pacing resulted in recovery of cardiac function and recovery of atrial tubule density to control values. Furthermore, when loaded with Fluo-8AM, calcium was firstly released along the tubules in the recovered myocytes, followed by propagation to the rest of the cell. Expression of BIN1, Tcap and MTM1 correlated with t-tubule density. Vectors encoding BIN1, Tcap and MTM1 were transiently expressed in neonatal rat ventricular myocytes. After
48hrs, overexpression of BIN1 led to the development of tubules, the structure of which was altered by coexpression with MTM1 and Tcap.

In conclusion, atrial t-tubules are lost in a sheep model of HF; this is associated with dyssynchronous calcium release. T-tubule associated proteins BIN1, MTM1 and Tcap also decrease during heart failure. Following recovery from HF t-tubule density, alongside calcium transient amplitude, is restored which could be due to up regulation of these proteins.