title: Electrotonic suppression of early afterdepolarizations in isolated rabbit Purkinje myocytes.
abstract: 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.
authors.affiliation: Cardiac Rhythm Management Laboratory and Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. djh@crml.uab.edu
authors.forename: D J
authors.initials: DJ
authors.lastname: Huelsing
authors.forename: K W
authors.initials: KW
authors.lastname: Spitzer
authors.forename: A E
authors.initials: AE
authors.lastname: Pollard
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D011690:Purkinje Fibers / Q000502:physiology*; D011817:Rabbits; D016276:Ventricular Function / Q000502:physiology*