Application of stochastic phenomenological modelling to cell-to-cell and beat-to-beat electrophysiological variability in cardiac tissue

John Walmsley*, Gary R. Mirams, Joe Pitt-Francis, Blanca Rodriguez, Kevin Burrage

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)

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 intercellular 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.
Original languageEnglish
Pages (from-to)325-336
JournalJournal of Theoretical Biology
Volume365
DOIs
Publication statusPublished - 21 Jan 2015

Keywords

  • Cardiac electrophysiology
  • Inter-cellular coupling
  • Stochastic simulation

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