The role of the transient outward current in action potential repolarization: A simulation study

The potassium transient outward current (I_to) is active only during the early plateau of the action potential (AP) and, therefore, its role in governing APD is controversial. The goal of this work is to characterize I_to from patch-clamp experiments in canine ventricular epicardial cells and demonstrate its influence in cardiac restitution using an AP mathematical model. Data from our experiments has been used to define a new mathematical model for I_to, which has been then inserted in the Decker et al. model for canine epicardial AP, substituting the original formulation of I_to. The new model predicts an increase in action potential duration (APD) when I_to is blocked, in accordance with recent experimental evidence. Inspection of the ionic currents in the simulations show that the blockade of I_to may indirectly affect other plateau ionic currents like L-type Calcium current (I_CaL) and the rapid component of the rectifier potassium current (I_Kr), producing an increment in the APD. These novel findings emphasize the importance of I_to in repolarization and suggest a potential role of I_to blockade in arrhythmogenesis.