title: Application of stochastic phenomenological modelling to cell-to-cell and beat-to-beat electrophysiological variability in cardiac tissue.
abstract: Variability in the action potential of isolated myocytes and tissue samples is observed in experimental studies. Variability is manifested as both differences in the action potential (AP) morphology between cells (extrinsic variability), and also 'intrinsic' or beat-to-beat variability of repolarization (BVR) in the AP duration of each cell. We studied the relative contributions of experimentally recorded intrinsic and extrinsic variability to dispersion of repolarization in tissue. We developed four cell-specific parameterizations of a phenomenological stochastic differential equation AP model exhibiting intrinsic variability using APs recorded from isolated guinea pig ventricular myocytes exhibiting BVR. We performed simulations in tissue using the four different model parameterizations in the presence and the absence of both intrinsic and extrinsic variability. We altered the coupling of the tissue to determine how inter-cellular coupling affected the dispersion of the AP duration in tissue. Both intrinsic and extrinsic variability were gradually revealed by reduction of tissue coupling. However, the recorded extrinsic variability between individual myocytes produced a greater degree of dispersion in repolarization in tissue than the intrinsic variability of each myocyte.
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, United Kingdom. Electronic address: j.walmsley@maastrichtuniversity.nl.
authors.forename: John
authors.initials: J
authors.lastname: Walmsley
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, United Kingdom.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Mirams
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, United Kingdom.
authors.forename: Joe
authors.initials: J
authors.lastname: Pitt-Francis
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, United Kingdom.
authors.forename: Blanca
authors.initials: B
authors.lastname: Rodriguez
authors.affiliation: Department of Computer Science, University of Oxford, Oxford, United Kingdom; School of Mathematical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Kevin
authors.initials: K
authors.lastname: Burrage
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003198:Computer Simulation; D055724:Electrophysiological Phenomena; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D008955:Models, Cardiovascular; D013269:Stochastic Processes; D013997:Time Factors
keywords: Cardiac electrophysiology; Inter-cellular coupling; Stochastic simulation