title: The dual effect of ephaptic coupling on cardiac conduction with heterogeneous expression of connexin 43.
abstract: Decreased and heterogeneous expression of connexin 43 (Cx43) are common features in animal heart failure models. Ephpatic coupling, which relies on the presence of junctional cleft space between the ends of adjacent cells, has been suggested to play a more active role in mediating intercellular electrical communication when gap junctions are reduced. To better understand the interplay of Cx43 expression and ephaptic coupling on cardiac conduction during heart failure, we performed numerical simulations on our model when Cx43 expression is reduced and heterogeneous. Under severely reduced Cx43 expression, we identified three new phenomena in the presence of ephaptic coupling: alternating conduction, in which ephaptic and gap junction-mediated mechanisms alternate; instability of planar fronts; and small amplitude action potential (SAP), which has a smaller potential amplitude than the normal action potential. In the presence of heterogeneous Cx43 expression, ephaptic coupling can either prevent or promote conduction block (CB) depending on the Cx43 knockout (Cx43KO) content. When Cx43KO content is relatively high, ephaptic coupling reduces the probabilities of CB. However, ephaptic coupling promotes CB when Cx43KO and wild type cells are mixed in roughly equal proportion, which can be attributed to an increase in current-to-load mismatch.
authors.affiliation: School of Mathematics, University of Minnesota, 206 Church St. SE, Minneapolis, MN 55455, United States.
authors.forename: Ning
authors.initials: N
authors.lastname: Wei
authors.affiliation: School of Mathematics, University of Minnesota, 206 Church St. SE, Minneapolis, MN 55455, United States.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 312 Church St. SE, 6-128 Nils Hasselmo Hall, Minneapolis, MN 55455, United States. Electronic address: talkacal@umn.edu.
authors.forename: Elena G
authors.initials: EG
authors.lastname: Tolkacheva
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000465:Algorithms; D000818:Animals; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D006321:Heart / Q000502:physiology; D006329:Heart Conduction System / Q000378:metabolism / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism; D018345:Mice, Knockout; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009431:Neural Conduction / Q000235:genetics / Q000502:physiology*
chemical_list: D018031:Connexin 43; D007473:Ion Channels
keywords: Alternating conduction; Bidomain model; Conduction block; Heterogeneous connexin 43; Instability of planar fronts; Small amplitude action potential