Fast-slow analysis and bifurcations in the generation of the early afterdepolarization phenomenon in a realistic mathematical human ventricular myocyte model.

Abstract

Early afterdepolarizations (EADs) are spontaneous oscillations in membrane potential that occur during the repolarization phase of the action potential. EADs can trigger ventricular arrhythmias, such as Torsades de Pointes, in patients with long QT syndromes. Understanding the theoretical mechanisms behind EAD generation and developing strategies to suppress them are crucial. In this study, we employed bifurcation analysis along with a new fast-slow decomposition method on the O'Hara model of human ventricular myocytes. Our goal was to examine how the calcium ion concentration in the network sarcoplasmic reticulum (NSR) influences the generation of EADs in the context of reduced rapid delayed rectifier K+ current. Our findings identified nine distinct EAD states that coexist and can be controlled by slight adjustments to the NSR calcium ion concentration at a single time point.