Memory in a fractional-order cardiomyocyte model alters voltage- and calcium-mediated instabilities

Cardiac myocyte electrical activity is traditionally approximated with ideal resistor-capacitor circuit networks. However, non-ideal circuit components may provide a more realistic approximation of excitable cell behavior. Such non-ideal circuit components are governed by fractional-order dynamics and contribute capacitive memory effects to the excitable cell system. Our prior work has detailed the effects of cell membrane-derived capacitive memory in a minimal cardiac model driven by voltage instabilities, and capacitive memory has been shown to shorten the action potential duration (APD) and suppress a beat-to-beat alternation in the APD known as alternans. In this study, we investigate the effects of memory in a biophysically detailed cardiac model that accounts for detailed representations of intracellular calcium cycling and transmembrane voltage dynamics. We perform simulations of varying fractional-order and pacing cycle length and investigate conditions in which alternans is driven by either voltage- or calcium-mediated instabilities. We found that capacitive memory suppresses alternans when calcium-mediated. Interestingly, when mediated by voltage-driven instabilities, memory effects induced a calcium instability that in turn promoted alternans under most conditions. In summary, capacitive memory due to fractional-order dynamics alters electrical signaling in cardiac cells in a manner than may either promote or suppress instabilities. (C) 2020 Elsevier B.V. All rights reserved.