Role of the late sodium current in arrhythmias related to low repolarization reserve

The prolongation of action potential duration (APD) is usually related to conditions of low repolarization reserve and leads to long QT syndrome. In these situations, an unbalance between currents can fire early after depolarizations (EADs). This repolarizing disorder has been observed in heart failure situations, where the late sodium current (I_NaL) has an important role. In this work we evaluate the effects of I_NaL enhancement in the ventricular wall under normal conditions and we analyze the role of I_NaL under pathological conditions prone to EADs generation. Human I_NaL was formulated and introduced in ten Tusscher AP model. Our results show that the increase in the maximum conductance of I_NaL prolongs APD in a rate-dependent manner especially in M cells. A 10-fold increase of I_NaL prolongs APD in 35 %, 44 % and 80 % for a stimulation rate of 1 Hz in epicardium, endocardium and M cells, respectively. Finally, the enhancement of I_NaL under conditions of low repolarization reserve led to EADs formation in M cells.