Slow [Na] dynamics impacts arrhythmogenesis and spiral wave reentry in cardiac myocyte ionic model.

Accumulation of intracellular Na is gaining recognition as an important regulator of cardiac myocyte electrophysiology. The intracellular Na concentration can be an important determinant of the cardiac action potential duration, can modulate the tissue-level conduction of excitation waves, and can alter vulnerability to arrhythmias. Mathematical models of cardiac electrophysiology often incorporate a dynamic intracellular Na concentration, which changes much more slowly than the remaining variables. We investigated the dependence of several arrhythmogenesis-related factors on [Na] in a mathematical model of the human atrial action potential. In cell simulations, we found that [Na] accumulation stabilizes the action potential duration to variations in several conductances and that the slow dynamics of [Na] impacts bifurcations to pro-arrhythmic afterdepolarizations, causing intermittency between different rhythms. In long-lasting tissue simulations of spiral wave reentry, [Na] becomes spatially heterogeneous with a decreased area around the spiral wave rotation center. This heterogeneous region forms a functional anchor, resulting in diminished meandering of the spiral wave. Our findings suggest that slow, physiological, rate-dependent variations in [Na] may play complex roles in cellular and tissue-level cardiac dynamics.