Effect of gap junction uncoupling on spatial dispersion of action potential duration at sites of abrupt tissue expansion

Spatial dispersion of action potential duration has been linked to arrhythmogenesis in the diseased heart; however, the complex dynamic between repolarization dynamics and microstructural heterogeneity in critical regimes is largely unknown. The objective of this study was to use microstructural computer models of adult monolayers to study the effect of abrupt tissue expansion and gap junction uncoupling on dispersion of action potential duration (APD) during premature stimulation. Two-dimensional discrete and equivalent continuous computer models (dx=10 μm, dy=10 μm) of ventricular monolayers with isthmus strands connected to a load region were generated. In the discrete model, gap junctions (gj) with a value between 0.005 μS and 0.50 μS were uniformly distributed around individual cells. In strands with a width of 300 μm, decreasing gap junction coupling in the discrete model increased variation in APD at the site of abrupt expansion by as much as 6 ms and changed the APD profile at the expansion site from an elliptical to a bipolar configuration. In narrow strands with a width of 60 μm, uniformly decreasing coupling in both the strand and the load increased variation in APD by as much as 14 ms and facilitated propagation at the expansion site. The equivalent continuous model could not reproduce microstructural variations in APD, the pattern of conduction block observed in moderately coupled tissue or the conduction delay observed at the site of abrupt expansion.