Dataset Information

Shannon2004_VentricularMyocyte

ABSTRACT: This a model from the article: A mathematical treatment of integrated Ca dynamics within the ventricular myocyte. Shannon TR, Wang F, Puglisi J, Weber C, Bers DM. Biophys J. 15347581 , doi: 10.1529/biophysj.104.047449 Abstract: We have developed a detailed mathematical model for Ca2+ handling and ionic currents in the rabbit ventricular myocyte. The objective was to develop a model that: 1), accurately reflects Ca-dependent Ca release; 2), uses realistic parameters, particularly those that concern Ca transport from the cytosol; 3), comes to steady state; 4), simulates basic excitation-contraction coupling phenomena; and 5), runs on a normal desktop computer. The model includes the following novel features: 1), the addition of a subsarcolemmal compartment to the other two commonly formulated cytosolic compartments (junctional and bulk) because ion channels in the membrane sense ion concentrations that differ from bulk; 2), the use of realistic cytosolic Ca buffering parameters; 3), a reversible sarcoplasmic reticulum (SR) Ca pump; 4), a scheme for Na-Ca exchange transport that is [Na]i dependent and allosterically regulated by [Ca]i; and 5), a practical model of SR Ca release including both inactivation/adaptation and SR Ca load dependence. The data describe normal electrical activity and Ca handling characteristics of the cardiac myocyte and the SR Ca load dependence of these processes. The model includes a realistic balance of Ca removal mechanisms (e.g., SR Ca pump versus Na-Ca exchange), and the phenomena of rest decay and frequency-dependent inotropy. A particular emphasis is placed upon reproducing the nonlinear dependence of gain and fractional SR Ca release upon SR Ca load. We conclude that this model is more robust than many previously existing models and reproduces many experimental results using parameters based largely on experimental measurements in myocytes. This model was taken from the CellML repository and automatically converted to SBML. The original model was: shannon, wang, puglisi, weber, bers, 2004, version04 The original CellML model was created by: Fink, Martin, Oxford University 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: Lukas Endler

PROVIDER: MODEL7914464799 | BioModels | 2005-01-01

REPOSITORIES: BioModels

ACCESS DATA

Publications

A mathematical treatment of integrated Ca dynamics within the ventricular myocyte.

Shannon Thomas R TR Wang Fei F Puglisi José J Weber Christopher C Bers Donald M DM

Biophysical journal 20040903 5

We have developed a detailed mathematical model for Ca2+ handling and ionic currents in the rabbit ventricular myocyte. The objective was to develop a model that: 1), accurately reflects Ca-dependent Ca release; 2), uses realistic parameters, particularly those that concern Ca transport from the cytosol; 3), comes to steady state; 4), simulates basic excitation-contraction coupling phenomena; and 5), runs on a normal desktop computer. The model includes the following novel features: 1), the addi ...[more]

PMID: 15347581

Similar Datasets

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: 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:Cardiac sarcoplasmic reticulum (SR) plays a central role in cellular Ca homeostasis, as does endoplasmic reticulum (ER) in the nonmuscle cell. The importance of SR Ca-handling function has led to detailed understanding of Ca-release and re-uptake protein complexes, but relatively little information regarding other known ER functions. We isolated cardiac membranes based upon their ability to efficiently accumulate Ca by the SR,ER-ATPase (SERCA-positive membranes), a process known to produce two characteristic SR membrane fractions: those enriched in known junctional SR markers, and those enriched in proteins originating from classic ER subdomains. Using standard proteomic techniques, we determined the SR proteins in three membrane preparations: 1) the highest-density SERCA-positive microsomes (HighSR); 2) the slightly less dense SERCA-positive microsomes that are constrained by a ryanodine-dependent leak (MedSR); and the original crude cardiac microsomes. Only a third of all crude microsomal proteins in heart were enriched in SERCA-positive membranes at least two fold. This protocol completely excluded known contractile, mitochondrial, sarcolemmal, and other major microsomal proteins, producing a far cleaner preparation of SR. Each SERCA-positive protein was distributed between HighSR and MedSR membrane vesicles in accordance with relative densities of SERCA2a versus ryanodine receptor. The distributions reinforced past findings on the distributions for several of the major known proteins. When combined with values for relative abundance, and enrichment over crude membranes, our protocol conveniently and effectively exposed multiple domains of the cardiac ER/SR. Most of the highly enriched and abundant cardiac SR/ER proteins represent proteins that have received little research attention. The data generate a useful quantitative analysis of intracellular membrane structure and function within cardiomyocytes, and may provide a reliable way of gauging broader changes in cardiac SR.

Project description:This a model from the article: A model of the guinea-pig ventricular cardiac myocyte incorporating a transverse-axial tubular system. Pásek M, Simurda J, Orchard CH, Christé G. Prog Biophys Mol Biol. 2008 Jan-Apr;96(1-3):258-80. 17888503 , Abstract: A model of the guinea-pig cardiac ventricular myocyte has been developed that includes a representation of the transverse-axial tubular system (TATS), including heterogeneous distribution of ion flux pathways between the surface and tubular membranes. The model reproduces frequency-dependent changes of action potential shape and intracellular ion concentrations and can replicate experimental data showing ion diffusion between the tubular lumen and external solution in guinea-pig myocytes. The model is stable at rest and during activity and returns to rested state after perturbation. Theoretical analysis and model simulations show that, due to tight electrical coupling, tubular and surface membranes behave as a homogeneous whole during voltage and current clamp (maximum difference 0.9 mV at peak tubular INa of -38 nA). However, during action potentials, restricted diffusion and ionic currents in TATS cause depletion of tubular Ca2+ and accumulation of tubular K+ (up to -19.8% and +3.4%, respectively, of bulk extracellular values, at 6 Hz). These changes, in turn, decrease ion fluxes across the TATS membrane and decrease sarcoplasmic reticulum (SR) Ca2+ load. Thus, the TATS plays a potentially important role in modulating the function of guinea-pig ventricular myocyte in physiological conditions. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Pásek M, Simurda J, Orchard CH, Christé G. (2008) - version03 The original CellML model was created by: Lloyd, Catherine, May c.lloyd@aukland.ac.nz The University of Auckland The 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.

Project description: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.

Project description:This a model from the article: Synergism of coupled subsarcolemmal Ca2+ clocks and sarcolemmal voltage clocks confers robust and flexible pacemaker function in a novel pacemaker cell model. Maltsev VA, Lakatta EG. Am J Physiol Heart Circ Physiol 2009 Mar;296(3):H594-615 19136600 , Abstract: Recent experimental studies have demonstrated that sinoatrial node cells (SANC) generate spontaneous, rhythmic, local subsarcolemmal Ca(2+) releases (Ca(2+) clock), which occur during late diastolic depolarization (DD) and interact with the classic sarcolemmal voltage oscillator (membrane clock) by activating Na(+)-Ca(2+) exchanger current (I(NCX)). This and other interactions between clocks, however, are not captured by existing essentially membrane-delimited cardiac pacemaker cell numerical models. Using wide-scale parametric analysis of classic formulations of membrane clock and Ca(2+) cycling, we have constructed and initially explored a prototype rabbit SANC model featuring both clocks. Our coupled oscillator system exhibits greater robustness and flexibility than membrane clock operating alone. Rhythmic spontaneous Ca(2+) releases of sarcoplasmic reticulum (SR)-based Ca(2+) clock ignite rhythmic action potentials via late DD I(NCX) over much broader ranges of membrane clock parameters [e.g., L-type Ca(2+) current (I(CaL)) and/or hyperpolarization-activated ("funny") current (I(f)) conductances]. The system Ca(2+) clock includes SR and sarcolemmal Ca(2+) fluxes, which optimize cell Ca(2+) balance to increase amplitudes of both SR Ca(2+) release and late DD I(NCX) as SR Ca(2+) pumping rate increases, resulting in a broad pacemaker rate modulation (1.8-4.6 Hz). In contrast, the rate modulation range via membrane clock parameters is substantially smaller when Ca(2+) clock is unchanged or lacking. When Ca(2+) clock is disabled, the system parametric space for fail-safe SANC operation considerably shrinks: without rhythmic late DD I(NCX) ignition signals membrane clock substantially slows, becomes dysrhythmic, or halts. In conclusion, the Ca(2+) clock is a new critical dimension in SANC function. A synergism of the coupled function of Ca(2+) and membrane clocks confers fail-safe SANC operation at greatly varying rates. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Maltsev VA, Lakatta EG. (2009) - version=1.0 The original CellML model was created by: Catherine Lloyd c.lloyd@auckland.ac.nz 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.

Dataset Information

Shannon2004_VentricularMyocyte

Publications

A mathematical treatment of integrated Ca dynamics within the ventricular myocyte.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure