Ion Channel Memory Drives Cardiac Early Afterdepolarizations in Fractional Models

Understanding how past factors influence ion channel kinetics is essential for understanding complex phenomena in cardiac electrophysiology, such as early afterdepolarizations (EADs), which are abnormal depolarizations during the action potential plateau associated with life-threatening arrhythmias. We developed a mathematical framework that extends Hodgkin-Huxley type equations with gamma Mittag-Leffler distributed delays, using tools from Fractional Calculus. Traditional memoryless two-variable models fail to reproduce EADs. Our approach modifies FitzHugh-Nagumo, Mitchell-Schaeffer, and Karma cardiac models, enabling the generation of EADs in each of them. We analyze the emergence of these oscillations by discussing the fractional parameters and the mean and variance of the memory kernels. Stability observations are also presented.