Intercellular conductance variability influences early repolarization potentials in a model of the myocardial tissue with stochastic architecture

Early repolarization anomalies on the electrocardiogram have been recently associated with malignant arrhythmias and sudden cardiac death in a variety of human populations. In order to increase their predictive power, there is a continuing need for detailed documentation of their possible electrophys-iological mechanism. We aimed to evaluate the influence of electrotonic modulation of intercellular flow of currents via gap junctions on action potential (AP) shapes. We used a Faber-Rudy membrane model of the guinea pig ventricular cardiomyocyte, modified through the introduction of Markov models for I
Kr
and parameter adjustment to achieve a more human-like model of the midmyocardium cells. The Faber-Rudy model is an extensively studied and verified finite difference model of the transmembrane ion currents and potential. We generated a stochastic 2D model (model N) of a strip of tissue consisting of three parallel chains of interconnected cells. The length of cells were random (0.07–0.13 mm). The gap junction density was considered constant, thus the actual intercellular conducance (IC) was governed by the interconnection architecture. All other electrophysiological parameters were identical in all cells. The first three cells at the left of the strip were simultaneously paced, resulting in propagating action potentials. One action potential was recorded in each cell. Another model (H) was generated in the same way but with lower IC. APs from each model were plotted, synchronized according to the start of phase 0, allowing visual estimation of their shape variability. The random distribution of the IC resulted in substantial variability of the AP notch and some variability of the AP duration. This effect was stronger when cells were relatively decoupled (H) as in the hypertrophic and ischaemic myocardium. These results suggest that modulation of electrotonic coupling during and after ventricular depolarization might be one of the causes influencing early repolarization potentials, particularly with parameters corresponding to common pathological circumstances.