MEMBRANE AND TISSUE LEVEL CONTRIBUTIONS TO PURKINJE-VENTRICULAR INTERACTIONS: A MODEL STUDY

Abstract

Purkinje-to-ventricular (P-to-V) propagation and electrotonic modulation of repolarization at discrete Purkinje-ventricular junctions (PVJs) depend on differences in the ionic currents and tissue structure of the P network and the V myocardium. We used computer simulations to assess these membrane and tissue level contributions to P-V interactions. At the membrane level, we used the DiFrancesco-Noble membrane equations to model P ionic kinetics and the Luo-Rudy dynamic membrane equations to model V ionic kinetics. At the tissue level, we modeled the P network as a layer of branching cables, and we modeled a single myocardial sheet with an anisotropic layer of excitable cells. P-to-V propagation was enhanced at the tissue level when multiple wavefronts in the branching P network collided at the PVJ. At the membrane level, P-to-V propagation was enhanced by a reduced transient outward current (Ito) in the P layer. Repolarization at the PVJ was also modulated by both membrane and tissue level contributions. Under nominal conditions, action potential duration (APD) shortened in the P layer and prolonged in the V layer. However, when the V mass was reduced, both P and V cell APDs shortened during coupling with nominal Ito. Subsequent Ito inhibition restored coupling-induced prolongation of the V action potential in the reduced V mass. These results suggest that under physiologic conditions, both membrane and tissue level contributions to P-V interactions are important, while membrane level contributions become even more important under pathologies that reduce the difference in P and V tissue size, particularly in the setting of healed myocardial infarction.