Livshitz2007_CardiacMyocytes

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Short description

This a model from the article:
Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents.
Livshitz LM, Rudy Y. Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H2854-66. 17277017 ,
Abstract:
Alternans of cardiac repolarization is associated with arrhythmias and sudden death. At the cellular level, alternans involves beat-to-beat oscillation of the action potential (AP) and possibly Ca(2+) transient (CaT). Because of experimental difficulty in independently controlling the Ca(2+) and electrical subsystems, mathematical modeling provides additional insights into mechanisms and causality. Pacing protocols were conducted in a canine ventricular myocyte model with the following results: 1) CaT alternans results from refractoriness of the sarcoplasmic reticulum Ca(2+) release system; alternation of the L-type calcium current has a negligible effect; 2) CaT-AP coupling during late AP occurs through the sodium-calcium exchanger and underlies AP duration (APD) alternans; 3) increased Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity extends the range of CaT and APD alternans to slower frequencies and increases alternans magnitude; its decrease suppresses CaT and APD alternans, exerting an antiarrhythmic effect; and 4) increase of the rapid delayed rectifier current (I(Kr)) also suppresses APD alternans but without suppressing CaT alternans. Thus CaMKII inhibition eliminates APD alternans by eliminating its cause (CaT alternans) while I(Kr) enhancement does so by weakening CaT-APD coupling. The simulations identify combined CaMKII inhibition and I(Kr) enhancement as a possible antiarrhythmic intervention.

This model was taken from the CellML repository and automatically converted to SBML.
The original model was: Livshitz LM, Rudy Y. (2007) - version01
The original CellML model was created by:
Noble, Penny,
penny.noble@dpag.ox.ac.uk
The University of Oxford

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Format
SBML (L2V3)
Related Publication
  • Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents.
  • Livshitz LM, Rudy Y
  • American journal of physiology. Heart and circulatory physiology , 6/ 2007 , Volume 292 , pages: H2854-66
  • Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, Missouri 63130-4899, USA.
  • Alternans of cardiac repolarization is associated with arrhythmias and sudden death. At the cellular level, alternans involves beat-to-beat oscillation of the action potential (AP) and possibly Ca(2+) transient (CaT). Because of experimental difficulty in independently controlling the Ca(2+) and electrical subsystems, mathematical modeling provides additional insights into mechanisms and causality. Pacing protocols were conducted in a canine ventricular myocyte model with the following results: 1) CaT alternans results from refractoriness of the sarcoplasmic reticulum Ca(2+) release system; alternation of the L-type calcium current has a negligible effect; 2) CaT-AP coupling during late AP occurs through the sodium-calcium exchanger and underlies AP duration (APD) alternans; 3) increased Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity extends the range of CaT and APD alternans to slower frequencies and increases alternans magnitude; its decrease suppresses CaT and APD alternans, exerting an antiarrhythmic effect; and 4) increase of the rapid delayed rectifier current (I(Kr)) also suppresses APD alternans but without suppressing CaT alternans. Thus CaMKII inhibition eliminates APD alternans by eliminating its cause (CaT alternans) while I(Kr) enhancement does so by weakening CaT-APD coupling. The simulations identify combined CaMKII inhibition and I(Kr) enhancement as a possible antiarrhythmic intervention.
Contributors
Vijayalakshmi Chelliah

Metadata information

is
BioModels Database MODEL0406270966
isDescribedBy
PubMed 17277017
hasTaxon
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
occursIn
Brenda Tissue Ontology cardiac muscle fiber
Curation status
Non-curated
Original model(s)
http://www.cellml.org/models/livshitz_rudy_2007_version01
  • Model originally submitted by : Vijayalakshmi Chelliah
  • Submitted: Apr 22, 2009 6:59:58 PM
  • Last Modified: Apr 22, 2009 6:59:58 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Apr 22, 2009 6:59:58 PM
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Current version of Livshitz2007_CardiacMyocytes
  • Version: 1 public model Download this version
    • Submitted on: Apr 22, 2009 6:59:58 PM
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Original import of Livshitz2007_CardiacMyocytes