Conduction at the Purkinje-ventricular junction (PVJ) demonstrates unidirectional block under both physiological and pathophysiological conditions. Although this block is typically attributed to multidimensional electrotonic interactions, we examined possible membrane-level contributions using single, isolated rabbit Purkinje (P) and ventricular (V) myocytes coupled by an electronic circuit. When we varied the junctional resistance ( R j) between paired V myocytes, conduction block occurred at lower R j values during conduction from the smaller to larger myocyte (115 ± 59 MΩ) than from the larger to smaller myocyte (201 ± 51 MΩ). In Purkinje-ventricular myocyte pairs, however, block occurred at lower R j values during P-to-V conduction (85 ± 39 MΩ) than during V-to-P conduction (912 ± 175 MΩ), although there was little difference in the mean cell size. Companion computer simulations, performed to examine how the early plateau currents affected conduction, showed that P-to-V block occurred at lower R j values when the transient outward current was increased or the calcium current was decreased in the model P cell. These results suggest that intrinsic differences in phase 1 repolarization can contribute to unidirectional block at the PVJ.

Many studies suggest that early afterdepolarizations (EADs) arising from Purkinje fibers initiate triggered arrhythmias under pathological conditions. However, electrotonic interactions between Purkinje and ventricular myocytes may either facilitate or suppress EAD formation at the Purkinje-ventricular interface. To determine conditions that facilitated or suppressed EADs during Purkinje-ventricular interactions, we coupled single Purkinje myocytes and aggregates isolated from rabbit hearts to a passive model cell via an electronic circuit with junctional resistance (R(j)). The model cell had input resistance (R(m,v)) of 50 M Omega, capacitance of 39 pF, and a variable rest potential (V(rest,v)). EADs were induced in Purkinje myocytes during superfusion with 1 microM isoproterenol. Coupling at high R(j) to normally polarized V(rest,v) established a repolarizing coupling current during all phases of the Purkinje action potential. This coupling current preferentially suppressed EADs in single cells with mean membrane resistance (R(m,p)) of 297 M Omega, whereas EAD suppression in larger aggregates with mean R(m,p) of 80 M Omega required larger coupling currents. In contrast, coupling to elevated V(rest,v) established a depolarizing coupling current during late phase 2, phase 3, and phase 4 that facilitated EAD formation and induced spontaneous activity in single Purkinje myocytes and aggregates. These results have important implications for arrhythmogenesis in the infarcted heart when reduction of the ventricular mass due to scarring alters the R(m,p)-to-R(m,v) ratio and in the ischemic heart when injury currents are established during coupling between polarized Purkinje myocytes and depolarized ventricular myocytes.

Purkinje-ventricular junctions (PVJs) have been implicated as potential sites of arrhythmogenesis, in part because of the dispersion of action potential duration (APD) between Purkinje (P) and ventricular (V) myocytes. To characterize electrotonic modulation of APD as a function of junctional resistance ( R j), we coupled single isolated rabbit P and V myocytes with an electronic circuit. In seven of eight PV myocyte pairs, both APDs shortened on coupling at R j = 50 MΩ. This was in contrast to modulation of APD in paired ventricular myocytes, which demonstrated APD shortening of the intrinsically longer action potential and APD prolongation of the intrinsically shorter action potential. Companion computer simulations, performed to suggest possible mechanisms for the paradoxical shortening of the V action potential in paired P and V myocytes, showed that the difference in intrinsic peak plateau potentials ( V pp) of the P and V myocytes determined whether the V action potential shortened or prolonged on coupling. This difference in V pp caused a large, repolarizing coupling current to flow to the V myocyte, contributing to early inactivation of the L-type calcium current and early activation of the inward rectifier current. These results suggest that intrinsic differences in phase 1 repolarization could yield differing patterns of APD shortening or prolongation in the network of subendocardial PVJs, leaving some PVJs vulnerable to conduction of premature stimuli while other PVJs remain refractory.