Dataset Information

Faber2000_LRmodel_CardiacMyocytes

ABSTRACT: This a model from the article: Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study. Faber GM, Rudy Y. Biophys J 2000 May;78(5):2392-404 10777735 , Abstract: Sodium overload of cardiac cells can accompany various pathologies and induce fatal cardiac arrhythmias. We investigate effects of elevated intracellular sodium on the cardiac action potential (AP) and on intracellular calcium using the Luo-Rudy model of a mammalian ventricular myocyte. The results are: 1) During rapid pacing, AP duration (APD) shortens in two phases, a rapid phase without Na(+) accumulation and a slower phase that depends on [Na(+)](i). 2) The rapid APD shortening is due to incomplete deactivation (accumulation) of I(Ks). 3) The slow phase is due to increased repolarizing currents I(NaK) and reverse-mode I(NaCa), secondary to elevated [Na(+)](i). 4) Na(+)-overload slows the rate of AP depolarization, allowing time for greater I(Ca(L)) activation; it also enhances reverse-mode I(NaCa). The resulting increased Ca(2+) influx triggers a greater [Ca(2+)](i) transient. 5) Reverse-mode I(NaCa) alone can trigger Ca(2+) release in a voltage and [Na(+)](i)-dependent manner. 6) During I(NaK) block, Na(+) and Ca(2+) accumulate and APD shortens due to enhanced reverse-mode I(NaCa); contribution of I(K(Na)) to APD shortening is negligible. By slowing AP depolarization (hence velocity) and shortening APD, Na(+)-overload acts to enhance inducibility of reentrant arrhythmias. Shortened APD with elevated [Ca(2+)](i) (secondary to Na(+)-overload) also predisposes the myocardium to arrhythmogenic delayed afterdepolarizations. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Faber GM, Rudy Y. (2000) - version06 The original CellML model was created by: Ashton, Jesse, j.ashton@aukland.ac.nz The University of Auckland Auckland Bioengineering Institute This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

SUBMITTER: Vijayalakshmi Chelliah

PROVIDER: MODEL0912153452 | BioModels | 2005-01-01

REPOSITORIES: BioModels

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Publications

Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study.

Faber G M GM Rudy Y Y

Biophysical journal 20000501 5

Sodium overload of cardiac cells can accompany various pathologies and induce fatal cardiac arrhythmias. We investigate effects of elevated intracellular sodium on the cardiac action potential (AP) and on intracellular calcium using the Luo-Rudy model of a mammalian ventricular myocyte. The results are: 1) During rapid pacing, AP duration (APD) shortens in two phases, a rapid phase without Na(+) accumulation and a slower phase that depends on [Na(+)](i). 2) The rapid APD shortening is due to inc ...[more]

PMID: 10777735

Similar Datasets

Project 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 This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Project description:This a model from the article: A novel computational model of the human ventricular action potential and Ca transient. Grandi E, Pasqualini FS, Bers DM. J Mol Cell Cardiol 2010 Jan;48(1):112-21 19835882 , Abstract: We have developed a detailed mathematical model for Ca handling and ionic currents in the human ventricular myocyte. Our aims were to: (1) simulate basic excitation-contraction coupling phenomena; (2) use realistic repolarizing K current densities; (3) reach steady-state. The model relies on the framework of the rabbit myocyte model previously developed by our group, with subsarcolemmal and junctional compartments where ion channels sense higher [Ca] vs. bulk cytosol. Ion channels and transporters have been modeled on the basis of the most recent experimental data from human ventricular myocytes. Rapidly and slowly inactivating components of I(to) have been formulated to differentiate between endocardial and epicardial myocytes. Transmural gradients of Ca handling proteins and Na pump were also simulated. The model has been validated against a wide set of experimental data including action potential duration (APD) adaptation and restitution, frequency-dependent increase in Ca transient peak and [Na](i). Interestingly, Na accumulation at fast heart rate is a major determinant of APD shortening, via outward shifts in Na pump and Na-Ca exchange currents. We investigated the effects of blocking K currents on APD and repolarization reserve: I(Ks) block does not affect the former and slightly reduces the latter; I(K1) blockade modestly increases APD and more strongly reduces repolarization reserve; I(Kr) blockers significantly prolong APD, an effect exacerbated as pacing frequency is decreased, in good agreement with experimental results in human myocytes. We conclude that this model provides a useful framework to explore excitation-contraction coupling mechanisms and repolarization abnormalities at the single myocyte level. Copyright 2009 Elsevier Inc. All rights reserved. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Grandi E, Pasqualini FS, Bers DM. (2009) - version=1.0 The original CellML model was created by: Geoffrey Nunns gnunns1@jhu.edu The University of Auckland This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Project description:This a model from the article: A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Luo CH, Rudy Y. Circ Res 1994 Jun;74(6):1071-96 7514509 , Abstract: A mathematical model of the cardiac ventricular action potential is presented. In our previous work, the membrane Na+ current and K+ currents were formulated. The present article focuses on processes that regulate intracellular Ca2+ and depend on its concentration. The model presented here for the mammalian ventricular action potential is based mostly on the guinea pig ventricular cell. However, it provides the framework for modeling other types of ventricular cells with appropriate modifications made to account for species differences. The following processes are formulated: Ca2+ current through the L-type channel (ICa), the Na(+)-Ca2+ exchanger, Ca2+ release and uptake by the sarcoplasmic reticulum (SR), buffering of Ca2+ in the SR and in the myoplasm, a Ca2+ pump in the sarcolemma, the Na(+)-K+ pump, and a nonspecific Ca(2+)-activated membrane current. Activation of ICa is an order of magnitude faster than in previous models. Inactivation of ICa depends on both the membrane voltage and [Ca2+]i. SR is divided into two subcompartments, a network SR (NSR) and a junctional SR (JSR). Functionally, Ca2+ enters the NSR and translocates to the JSR following a monoexponential function. Release of Ca2+ occurs at JSR and can be triggered by two different mechanisms, Ca(2+)-induced Ca2+ release and spontaneous release. The model provides the basis for the study of arrhythmogenic activity of the single myocyte including afterdepolarizations and triggered activity. It can simulate cellular responses under different degrees of Ca2+ overload. Such simulations are presented in our accompanying article in this issue of Circulation Research. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Luo CH, Rudy Y. (1994) - version02 This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Project description:This a model from the article: Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model. Hund TJ, Rudy Y. Circulation 2004 Nov 16;110(20):3168-74 15505083 , Abstract: BACKGROUND: Computational biology is a powerful tool for elucidating arrhythmogenic mechanisms at the cellular level, where complex interactions between ionic processes determine behavior. A novel theoretical model of the canine ventricular epicardial action potential and calcium cycling was developed and used to investigate ionic mechanisms underlying Ca2+ transient (CaT) and action potential duration (APD) rate dependence. METHODS AND RESULTS: The Ca2+/calmodulin-dependent protein kinase (CaMKII) regulatory pathway was integrated into the model, which included a novel Ca2+-release formulation, Ca2+ subspace, dynamic chloride handling, and formulations for major ion currents based on canine ventricular data. Decreasing pacing cycle length from 8000 to 300 ms shortened APD primarily because of I(Ca(L)) reduction, with additional contributions from I(to1), I(NaK), and late I(Na). CaT amplitude increased as cycle length decreased from 8000 to 500 ms. This positive rate-dependent property depended on CaMKII activity. CONCLUSIONS: CaMKII is an important determinant of the rate dependence of CaT but not of APD, which depends on ion-channel kinetics. The model of CaMKII regulation may serve as a paradigm for modeling effects of other regulatory pathways on cell function. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Hund TJ, Rudy Y. (2004) - version03 The original CellML model was created by: Noble, Penny penny.noble@dpag.ox.ac.uk University of Oxford This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Project description:Rationale: MicroRNAs play key roles in hypertrophic stress responses. miR-378(-3p) is a highly abundant, cardiomyocyte-enriched microRNA whose downregulation in pressure-overload has been suggested as detrimental to the heart. Previous studies have utilized systemic anti-miR or microRNA-encoding virus administration, and thus questions regarding the cardiomyocyte-autonomous roles of miR-378 remain. Objective: To examine whether persistent overexpression of miR-378 in cardiomyocytes alters the phenotype of the unstressed heart, whether its overexpression is beneficial or deleterious in the setting of pressure-overload, and to comprehensively identify its cardiomyocyte-specific effects on mRNA regulation. Methods and Results: Cardiac function was compared in young (10-12 week-old) mice overexpressing miR-378 in the heart under the control of the Myh6 promoter (alphaMHC-miR-378 mice), in older (40 week-old) mice and their age-matched wild-type controls. Older alphaMHC-miR-378 mice exhibited decreased fractional shortening and modest chamber dilation with an increase in cardiomyocyte length. When subjected to pressure-overload, cardiomyocyte length was increased in young alphaMHC-miR-378 mice, but fractional shortening declined precipitously over two weeks. Transcriptome profiling of wild-type and alphaMHC-miR-378 hearts in unstressed and pressure-overload conditions revealed dysregulation of several upstream metabolic and mitochondrial genes in alphaMHC-miR-378 hearts, compromising the reprogramming that occurs during early adaptation to pressure overload. Ago2 immunoprecipitation with mRNA sequencing revealed novel miR-378 cardiac mRNA targets including Akt1 and Epac2 and demonstrated the contextual nature of previously described miR-378 targeting events. Conclusions: Long-term upregulation of miR-378 levels in the heart is not innocuous and exacerbates contractile dysfunction in pressure-overload hypertrophy through numerous signaling mechanisms.

Dataset Information

Faber2000_LRmodel_CardiacMyocytes

Publications

Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study.

Similar Datasets

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