Recovering from cardiac action potential pathologies: a dynamic view

Abstract Many human cells fire plateau action potentials, from the endocrine system to the heart. For example, cardiac myocites may present perturbations of the plateau that are linked to the long QT syndrome and cardiac arrhythmia. Here, we provide a unified and minimalist dynamic explanation for some of the known forms of the loss of stability of the plateau, which are linked to these pathologies. One of these forms is a newly found non-chaotic aperiodic oscillation mode of autonomous plateau spikes. This happens via an infinite period bifurcation of the interspike interval. We accomplish this through a simple map model of the action potential containing two fast and one slow variables. This reveals a small set of ingredients for the observation of plateau anomalies, and allows us to propose different ways to recover from them by adjusting slow-fast timescales and the fast-fast coupling conductance. This integrated and generic view might provide insights for complex models with many variables and parameters. One of the predictions of the model is the existence of a critical value in the fast-fast coupling conductance below which cardiac spike anomalies completely disappear, regardless of other currents. Notwithstanding, excitable cardiac spikes stay away from prolongation if their slow variable time scales ratio between drive and recovery is less than one. These findings might help the future development of innovative treatments for the related diseases.