Computational study of the relative contribution of channel and gap junction remodelling on human atrial conduction during fibrillation

Chronic atrial fibrillation (AF) induces remodelling of both channel conductance and intercellular coupling in the human atrium. Effects of these changes and their relative contributions to atrial impulse conduction during fibrillation are unknown. In this study we constructed a virtual human atrial strand by incorporating the Nygren et al model of human atrial action potential into a 1-dimensional reaction diffusion partial differential equation. Experimental data on AF-induced changes of human atrial ionic channel conductances and kinetics and gap junction coupling were incorporated into a model to investigate their contributions and relative importance on conduction velocity (CV) at different rates. At low rates (stimulus interval SI>270 ms), AF-induced channel or gap junction remodelling reduced CV significantly. At high rates (SI<270 ms), channel remodelling increased CV while gap junction remodelling reduced the CV. When combined, channel and gap junction remodelling reduced CV additively. Spatial heterogeneities in gap junction coupling can produce intermittent conduction block.