Late Phase of Repolarization is Autoregenerative and Scales Linearly with Action Potential Duration in Mammals Ventricular Myocytes: A Model Study

Scaling of action potential (AP) duration (APD) in mammals of different size is a rather complex phenomenon, dominated by a regulatory type mechanism of ion channels expression. By means of simulations performed on six published mathematical models of cardiac ventricular APs of different mammals, it is shown that AP repolarization is autoregenerative in its later phase (ARRP) and that the duration of such phase scales linearly with APD. For each AP, a 3-D instantaneous time-voltage-current surface is constructed, which has been recently described in a more simplified model. This representation allows us to measure ARRP and to study the contribution to it for different ion currents. It has been found that the existence of an ARRP is not intrinsic to cardiac models formulation; one out of the six models does not show this phase. A linear correlation between ARRP duration and APD in the remaining models is also found. It is shown that ARRP neither simply depend on AP shape nor on APD. Though I_K1 current seems to be the main responsible for determining and modulating this phase, the mechanism by which ARRP scales linearly with APD remains unclear and raises further questions on the scaling strategies of cardiac repolarization in mammals.