Conductance heterogeneities induced by multistability in the dynamics of coupled cardiac gap junctions

Abstract

In this paper, we study the propagation of the cardiac action potential in a one-dimensional fiber, where cells are electrically coupled through gap junctions (GJs). We consider gap junctional gate dynamics that depend on the intercellular potential. We find that different GJs in the tissue can end up in two different states: a low conducting state and a high conducting state. We first present evidence of the dynamical multistability that occurs by setting specific parameters of the GJ dynamics. Subsequently, we explain how the multistability is a direct consequence of the GJ stability problem by reducing the dynamical system's dimensions. The conductance dispersion usually occurs on a large time scale, i.e., thousands of heartbeats. The full cardiac model simulations are computationally demanding, and we derive a simplified model that allows for a reduction in the computational cost of four orders of magnitude. This simplified model reproduces nearly quantitatively the results provided by the original full model. We explain the discrepancies between the two models due to the simplified model's lack of spatial correlations. This simplified model provides a valuable tool to explore cardiac dynamics over very long time scales. That is highly relevant in studying diseases that develop on a large time scale compared to the basic heartbeat. As in the brain, plasticity and tissue remodeling are crucial parameters in determining the action potential wave propagation's stability. (C) 2021 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).