Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Mathematical models of cardiac cells have become important tools for investigating the electrophysiological properties and behavior of the heart. As the number of published models increases, it becomes More difficult to choose a model appropriate for the conditions to be studied, especially when multiple models describing the species and region of the heart of interest are available. In this paper, we will review and compare two detailed ionic models of human atrial myocytes, the Nygren et al. model (NM) and the Courtemanche et al. model (CM). Although both models include the same transmembrane currents and are largely based on the same experimental data from human atrial cells, the two models exhibit vastly different properties, especially in their dynamical behavior, including restitution and memory effects. The CM produces pronounced rate adaptation of action potential duration (APD) with limited memory effects, while the NM exhibits strong rate dependence of resting membrane potential (RMP), limited APD restitution, and stronger memory, as well as delayed afterdepolarizations and auto-oscillatory behavior upon cessation of rapid pacing. Channel conductance modifications based on experimentally measured changes during atrial fibrillation modify rate adaptation and memory in both models, but do not change the primary rate-dependent properties of APD and RMP for the CM and NM, respectively. Two sets of proposed changes to the NM that yield a spike-and-dome action potential morphology qualitatively similar to the CM at slow pacing rates similarly do not change the underlying dynamics of the model. Moreover, interchanging the formulations of all transmembrane currents between the two models while leaving calcium handling and ionic concentrations intact indicates that the currents strongly influence memory and the rate adaptation of RMP, while intracellular calcium dynamics primarily determine APD rate adaptation. Our results suggest that differences in intracellular calcium handling between the two human atrial myocyte models are responsible for marked dynamical differences and may prevent reconciliation between the models by straightforward channel conductance modifications. (c) 2008 Elsevier Ltd. All rights reserved.