The contribution of ionic currents to rate-dependent action potential duration and pattern of reentry in a mathematical model of human atrial fibrillation

Young Seon Lee, Minki Hwang, Jun Seop Song, Changyong Li, Boyoung Joung, Eric A. Sobie, huinam pak

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Persistent atrial fibrillation (PeAF) in humans is characterized by shortening of action potential duration (APD) and attenuation of APD rate-adaptation. However, the quantitative influences of particular ionic current alterations on rate-dependent APD changes, and effects on patterns of reentry in atrial tissue, have not been systematically investigated. Using mathematical models of human atrial cells and tissue and performing parameter sensitivity analysis, we evaluated the quantitative contributions to action potential (AP) shortening and APD rate-adaptation of ionic current remodeling seen with PeAF. Ionic remodeling in PeAF was simulated by reducing L-type Ca2+ channel current (ICaL), increasing inward rectifier K+ current (IK1) and modulating five other ionic currents. Parameter sensitivity analysis, which quantified how each ionic current influenced APD in control and PeAF conditions, identified interesting results, including a negative effect of Na+/Ca2+ exchange on APD only in the PeAF condition. At high pacing rate (2 Hz), electrical remodeling in IK1 alone accounts for the APD reduction of PeAF, but at slow pacing rate (0.5 Hz) both electrical remodeling in ICaL alone (-70%) and IK1 alone (+100%) contribute equally to the APD reduction. Furthermore, AP rate-adaptation was affected by IKur in control and by INaCa in the PeAF condition. In a 2D tissue model, a large reduction (-70%) of ICaL becomes a dominant factor leading to a stable spiral wave in PeAF. Our study provides a quantitative and unifying understanding of the roles of ionic current remodeling in determining rate-dependent APD changes at the cellular level and spatial reentry patterns in tissue.

Original languageEnglish
Article numbere0150779
JournalPLoS One
Volume11
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1

Fingerprint

Reentry
action potentials
Atrial Fibrillation
Action Potentials
Theoretical Models
mathematical models
Tissue
Mathematical models
duration
Sensitivity analysis
Atrial Remodeling
shortenings
atrial fibrillation
calcium

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "The contribution of ionic currents to rate-dependent action potential duration and pattern of reentry in a mathematical model of human atrial fibrillation",
abstract = "Persistent atrial fibrillation (PeAF) in humans is characterized by shortening of action potential duration (APD) and attenuation of APD rate-adaptation. However, the quantitative influences of particular ionic current alterations on rate-dependent APD changes, and effects on patterns of reentry in atrial tissue, have not been systematically investigated. Using mathematical models of human atrial cells and tissue and performing parameter sensitivity analysis, we evaluated the quantitative contributions to action potential (AP) shortening and APD rate-adaptation of ionic current remodeling seen with PeAF. Ionic remodeling in PeAF was simulated by reducing L-type Ca2+ channel current (ICaL), increasing inward rectifier K+ current (IK1) and modulating five other ionic currents. Parameter sensitivity analysis, which quantified how each ionic current influenced APD in control and PeAF conditions, identified interesting results, including a negative effect of Na+/Ca2+ exchange on APD only in the PeAF condition. At high pacing rate (2 Hz), electrical remodeling in IK1 alone accounts for the APD reduction of PeAF, but at slow pacing rate (0.5 Hz) both electrical remodeling in ICaL alone (-70{\%}) and IK1 alone (+100{\%}) contribute equally to the APD reduction. Furthermore, AP rate-adaptation was affected by IKur in control and by INaCa in the PeAF condition. In a 2D tissue model, a large reduction (-70{\%}) of ICaL becomes a dominant factor leading to a stable spiral wave in PeAF. Our study provides a quantitative and unifying understanding of the roles of ionic current remodeling in determining rate-dependent APD changes at the cellular level and spatial reentry patterns in tissue.",
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The contribution of ionic currents to rate-dependent action potential duration and pattern of reentry in a mathematical model of human atrial fibrillation. / Lee, Young Seon; Hwang, Minki; Song, Jun Seop; Li, Changyong; Joung, Boyoung; Sobie, Eric A.; pak, huinam.

In: PLoS One, Vol. 11, No. 3, e0150779, 01.03.2016.

Research output: Contribution to journalArticle

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T1 - The contribution of ionic currents to rate-dependent action potential duration and pattern of reentry in a mathematical model of human atrial fibrillation

AU - Lee, Young Seon

AU - Hwang, Minki

AU - Song, Jun Seop

AU - Li, Changyong

AU - Joung, Boyoung

AU - Sobie, Eric A.

AU - pak, huinam

PY - 2016/3/1

Y1 - 2016/3/1

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AB - Persistent atrial fibrillation (PeAF) in humans is characterized by shortening of action potential duration (APD) and attenuation of APD rate-adaptation. However, the quantitative influences of particular ionic current alterations on rate-dependent APD changes, and effects on patterns of reentry in atrial tissue, have not been systematically investigated. Using mathematical models of human atrial cells and tissue and performing parameter sensitivity analysis, we evaluated the quantitative contributions to action potential (AP) shortening and APD rate-adaptation of ionic current remodeling seen with PeAF. Ionic remodeling in PeAF was simulated by reducing L-type Ca2+ channel current (ICaL), increasing inward rectifier K+ current (IK1) and modulating five other ionic currents. Parameter sensitivity analysis, which quantified how each ionic current influenced APD in control and PeAF conditions, identified interesting results, including a negative effect of Na+/Ca2+ exchange on APD only in the PeAF condition. At high pacing rate (2 Hz), electrical remodeling in IK1 alone accounts for the APD reduction of PeAF, but at slow pacing rate (0.5 Hz) both electrical remodeling in ICaL alone (-70%) and IK1 alone (+100%) contribute equally to the APD reduction. Furthermore, AP rate-adaptation was affected by IKur in control and by INaCa in the PeAF condition. In a 2D tissue model, a large reduction (-70%) of ICaL becomes a dominant factor leading to a stable spiral wave in PeAF. Our study provides a quantitative and unifying understanding of the roles of ionic current remodeling in determining rate-dependent APD changes at the cellular level and spatial reentry patterns in tissue.

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