Determinants of heterogeneity, excitation and conduction in the sinoatrial node: A model study

Ronit V. Oren, Colleen E Clancy

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The sinoatrial node (SAN) is a complex structure that exhibits anatomical and functional heterogeneity which may depend on: 1) The existence of distinct cell populations, 2) electrotonic influences of the surrounding atrium, 3) the presence of a high density of fibroblasts, and 4) atrial cells intermingled within the SAN. Our goal was to utilize a computer model to predict critical determinants and modulators of excitation and conduction in the SAN. We built a theoretical "non-uniform" model composed of distinct central and peripheral SAN cells and a "uniform" model containing only central cells connected to the atrium. We tested the effects of coupling strength between SAN cells in the models, as well as the effects of fibroblasts and interspersed atrial cells. Although we could simulate single cell experimental data supporting the "multiple cell type" hypothesis, 2D "non-uniform" models did not simulate expected tissue behavior, such as central pacemaking. When we considered the atrial effects alone in a simple homogeneous "uniform" model, central pacemaking initiation and impulse propagation in simulations were consistent with experiments. Introduction of fibroblasts in our simulated tissue resulted in various effects depending on the density, distribution, and fibroblast-myocyte coupling strength. Incorporation of atrial cells in our simulated SAN tissue had little effect on SAN electrophysiology. Our tissue model simulations suggest atrial electrotonic effects as plausible to account for SAN heterogeneity, sequence, and rate of propagation. Fibroblasts can act as obstacles, current sinks or shunts to conduction in the SAN depending on their orientation, density, and coupling.

Original languageEnglish (US)
Article numbere1001041
JournalPLoS Computational Biology
Volume6
Issue number12
DOIs
StatePublished - Dec 2010

Fingerprint

Sinoatrial Node
Conduction
Determinant
Excitation
Fibroblasts
Vertex of a graph
fibroblasts
Cell
Tissue
cells
Model
Electrophysiology
Propagation
Myocytes
Distinct
electrophysiology
Modulators
simulation
Cell Population
effect

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Ecology
  • Molecular Biology
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Computational Theory and Mathematics

Cite this

Determinants of heterogeneity, excitation and conduction in the sinoatrial node : A model study. / Oren, Ronit V.; Clancy, Colleen E.

In: PLoS Computational Biology, Vol. 6, No. 12, e1001041, 12.2010.

Research output: Contribution to journalArticle

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