Ionic and Electrotonic Contributions to Short-Term Ventricular Action Potential Memory: An In Silico Study

Electrical restitution (ER) is a determinant of cardiac repolarization stability and can be measured as steady action potential (AP) duration (APD) at different pacing rates-the so-called dynamic restitution (ERdyn) curve-or as APD changes after pre- or post-mature stimulations-the so-called standard restitution (ERs1s2) curve. Short-term AP memory (Ms) has been described as the slope difference between the ERdyn and ERs1s2 curves, and represents the information stored in repolarization dynamics due to previous pacing conditions. Although previous studies have shown its dependence on ion currents and calcium cycling, a systematic picture of these features is lacking. By means of simulations with a human ventricular AP model, I show that APD restitution can be described under randomly changing pacing conditions (ERrand) and Ms derived as the slope difference between ERdyn and ERrand. Thus measured, Ms values correlate with those measured using ERs1s2. I investigate the effect on Ms of modulating the conductance of ion channels involved in AP repolarization, and of abolishing intracellular calcium transient. I show that Ms is chiefly determined by ERdyn rather than ERrand, and that interventions that shorten/prolong APD tend to decrease/increase Ms.