title: Lessons learned about slow discontinuous conduction from models of impulse propagation.
abstract: Propagation of excitation in the heart involves action potential generation by cardiac cells and its propagation in the multicellular tissue. Action potential conduction is the outcome of complex interactions between cellular processes (membrane ion channels and transporters), electrical communication between cells, and the macroscopic architecture of cardiac tissue. This high level of complexity and non linearity requires computer modeling in order to elucidate mechanisms and explain experimentally observed behaviors. This article reviews studies that we have conducted in 1-dimensional models that contain both, cellular ionic processes and intercellular communication through gap junctions. We have defined and computed a quantitative measure of the robustness of conduction, the safety factor, as a function of gap junction coupling and showed that reduced coupling can support very slow and very safe conduction. Such conduction is highly discontinuous and is supported by the L-type calcium current. We also show that gap junction coupling and the associated load has a strong effect on spatial repolarization gradients in cardiac tissue.
authors.affiliation: Cardiac Bioelectricity and Arrhythmia Center (CBAC), Washington University in St Louis, St Louis, MO 63130-4899, USA. rudy@wustl.edu
authors.forename: Yoram
authors.initials: Y
authors.lastname: Rudy
mesh_terms: D000200:Action Potentials; D000818:Animals; D015220:Calcium Channels; D002450:Cell Communication; D003198:Computer Simulation; D017629:Gap Junctions; D006329:Heart Conduction System / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D015640:Ion Channel Gating; D008955:Models, Cardiovascular; D008962:Models, Theoretical; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac; D015222:Sodium Channels
chemical_list: D015220:Calcium Channels; D015222:Sodium Channels