title: Effects of fibroblast-myocyte coupling on cardiac conduction and vulnerability to reentry: A computational study.
abstract: BACKGROUND
  Recent experimental studies have documented that functional gap junctions form between fibroblasts and myocytes, raising the possibility that fibroblasts play roles in cardiac electrophysiology that extend beyond acting as passive electrical insulators.
  
  
  OBJECTIVE
  The purpose of this study was to use computational models to investigate how fibroblasts may affect cardiac conduction and vulnerability to reentry under different fibroblast-myocyte coupling conditions and tissue structures.
  
  
  METHODS
  Computational models of two-dimensional tissue with fibroblast-myocyte coupling were developed and numerically simulated. Myocytes were modeled by the phase I of the Luo-Rudy model, and fibroblasts were modeled by a passive model.
  
  
  RESULTS
  Besides slowing conduction by cardiomyocyte decoupling and electrotonic loading, fibroblast coupling to myocytes elevates myocyte resting membrane potential, causing conduction velocity to first increase and then decrease as fibroblast content increases, until conduction failure occurs. Fibroblast-myocyte coupling can also enhance conduction by connecting uncoupled myocytes. These competing effects of fibroblasts on conduction give rise to different conduction patterns under different fibroblast-myocyte coupling conditions and tissue structures. Elevation of myocyte resting potential due to fibroblast-myocyte coupling slows sodium channel recovery, which extends postrepolarization refractoriness. Owing to this prolongation of the myocyte refractory period, reentry was more readily induced by a premature stimulation in heterogeneous tissue models when fibroblasts were electrotonically coupled to myocytes compared with uncoupled fibroblasts acting as pure passive electrical insulators.
  
  
  CONCLUSIONS
  Fibroblasts affect cardiac conduction by acting as obstacles or by creating electrotonic loading and elevating myocyte resting potential. Functional fibroblast-myocyte coupling prolongs the myocyte refractory period, which may facilitate induction of reentry in cardiac tissue with fibrosis.
authors.affiliation: Department of Medicine-Cardiology, David Geffen School of Medicine at University of California, Los Angeles, California 90095, USA.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Xie
authors.forename: Alan
authors.initials: A
authors.lastname: Garfinkel
authors.forename: Patrizia
authors.initials: P
authors.lastname: Camelliti
authors.forename: Peter
authors.initials: P
authors.lastname: Kohl
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Qu
mesh_terms: D054849:Cardiac Electrophysiology; D002450:Cell Communication / Q000502:physiology; D003198:Computer Simulation; D005347:Fibroblasts / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000502:physiology*