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A list of (detailed, non-stochastic) action potential models, with links to papers, source code, CellML and Myokit implementations

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Action potential models

This is a list of published action potential models. Specifically, detailed models (not reduced or propagation focussed) without stochastics (no release units).

Key

Models are listed as year, followed by first author (or multiple if shared first authorship). Model names / nicknames (e.g. LR1) are provided separately under "known as". Ordering is year, then first author alphabetically.

Type

  • A Atrial
  • V Ventricular
  • P Purkinje
  • S SA node
  • N AV node
  • e embryonic stem cell
  • i induced pluripotent stem cell
  • d Developing cardiomyocyte, neonatal, embryonic

Species

  • C Canine
  • F Frog
  • G Guinea pig
  • H Human
  • K chicken
  • L Rat
  • M Mouse
  • P Pig
  • R Rabbit
  • m Mammal

Preparation

  • f recordings in fibres or other multicellular preparations, instead of isolated cells

Base A tentative "base" model is indicated. This can be a clear ancestor - with many equations and parameters inherited - but also a more vague "inspiration".

Code Where possible, indicate whether code is

  • "Original": used by the authors when writing the publication
  • "Official": an author-provided or endorsed translation to code, e.g. a CellML created during or just after publishing
  • "Updated": created by authors or others, with slight modifications or fixes to original code

Inclusion criteria

Models are included if they represent the dynamics of a single cell or, for early models, of a small, space-clamped, multicellular preparation. Models are omitted if they contain spatial propagation, either in larger tissues or by dividing the cell into a multitude of "calcium release units".

Whether or not a modification counts as a "model" is entirely subjective. No strict criteria are used here, just try to make it useful.

Sources

Some papers with model lists or model comparison:

Online model repositories and lists:

A number of software packages are referenced because they contain reference implementations of models.

  • Oxsoft Heart (1984-1999) was a DOS program released by Denis Noble and his group, and contained Noble-group models in that period. It was succeded by COR (and then OpenCOR) and CellML. The Oxsoft models were all converted to CellML.
  • LabHEART (2001-2022) was a Windows program built around Bers et al. models. It is archived at https://web.archive.org/web/20220615151709/http://www.labheart.org/
  • simBio (2005-2008) was a Windows program released by Sarai et al., and contained the "Kyoto model" family. It can still be downloaded from https://sourceforge.net/projects/simbio/files/simBio. It was succeded (I think) by e-Heart.
  • e-Heart (2014-present) is a Windows (visual basic) program released by Noma's group(?) it can be downloaded from http://www.eheartsim.com.

Not included in the main list

Some reductions and propagation models:

  • Fitzugh 1961 reduces HH to a "Bonhoeffer-Van der Pol" model
  • Nagumo 1962 makes Fitzhugh 1961 suitable for propagation
  • Morris & Lecar 1981 create a reduced HH-like model of a Ca-driven AP
  • Winfree 1991 provides a great overview of spiral wave models, including Belousov-Zhabotinsky
  • Varghese 1993 reduces DiFrancesco 1985
  • Karma 1993 reduces Noble 1962 and adapts for propagation
  • Aliev & Panfilov 1996
  • Endresen 1997 adapts Morris-Lecar for rabbit SAN
  • Fenton & Karma 1998 derive an FN-like model
  • Bernus 2002 reduces Priebe 1998
  • Fenton 2002 builds on Fenton 1998
  • Garny et al. 2003 implemented "a variety" of one-dimensional SAN models
  • Mitchell & Schaeffer 2003
  • Biktasheva 2006 reduces Courtemanche 1998
  • Cherry 2006 uses Fenton 2002
  • Simitev 2006 adapted Biktasheva 2006
  • Ten Tusscher 2006b reduces Ten Tusscher 2006
  • Bueno-Orovio 2008 adds an equation to Fenton 1998
  • Tran 2009 reduces Luo 1991
  • Aslanidi 2012 applied the Courtemanche and Nygren models on realistic anatomy
  • Balakrishnan 2015 develop a reduced whole heart model
  • Gray & Pathmanathan 2016 create a minimal but fully parametrisable AP model
  • Corrado 2017, Carrado & Niederer 2016, Corrado 2018
  • ...

Some CaRU stochastic/spatial models:

  • Rice et al 1999 used stochastic CaRUs (called FRUs in the paper)
  • Greenstein 2002 builds on Rice 1999 and Winslow 1999
  • Lovell et al 2004 created a SAN model with a spatial gradient of heterogeneity
  • Tanskanen 2005 builds on Greenstein 2002
  • Greenstein 2006 builds on Greenstein 2002
  • Flaim et al 2006 modified Greenstein 2006
  • Stern 2014 built a sparking SAN model based on Maltsev 2009
  • Voigt 2014 built a CaRU model based on Voigt 2013
  • Sutanto 2018 adapted the Voigt 2014 model
  • Maltsev 2022 build on Stern 2014

Some models with other features:

  • Seemann et al. 2003 extend Priebe-Beuckelman with force generation (partial derivative) equations

1962 Noble mPf

Base: HH1952 | In PMR | Paper Noble (1962) A Modification of the Hodgkin-Huxley Equations Applicable to Purkinje Fibre Action and Pacemaker Potentials

1966 Krause mVf

Krause, Antoni, Fleckenstein (1966) An electronic model for the formation of local and transmitted stimuli on the myocardium fibers based upon variable current-voltage characteristics for potassium and sodium ions

Note: In german. Can't find it online

1975 McAllister mPf

Base: Noble 1962 | In PMR | Paper McAllister, Noble, Tsien (1975) Reconstruction of the electrical activity of cardiac Purkinje fibres

Known as: McAllister-Noble-Tsien (MNT)

1977 Beeler mVf

Base: McAllister 1975 | In Myokit repo | In PMR | Paper Beeler, Reuter (1977) Reconstruction of the action potential of ventricular myocardial fibres

Known as: Beeler-Reuter (BR)

Modifications:

  • Adds INa j gate based on work w. Haas
  • ...

1980 Yanagihara RSf

Base: Mixed | In PMR | Paper Yanagihara, Noma, Irisawa (1980) Reconstruction of sino-atrial node pacemaker potential based on the voltage clamp experiments

1982 Bristow RSf

Base: McAllister 1975 | Paper Bristow, Clark (1982) A mathematical model of primary pacemaking cell in SA node of the heart

Known as: Bristow-Clark

1982 Irisawa RSf

Base: Yanagihara 1980 | Chapter Irisawa, Noma (1982) Pacemaker mechanisms of rabbit sinoatrial node cells, in: Bouman, Jongsma (Eds.), Cardiac Rate and Rhythm: Physiological, Morphological, and Developmental Aspects

Known as: Irisawa-Noma

1984 Noble mSf

Base: DiFrancesco 1985 | In PMR | Paper Noble, Noble (1984) A model of sino-atrial node electrical activity based on a modification of the DiFrancesco-Noble 1984 equations

Known as: Noble-Noble model

Note: This is an adaptation of the DiFrancesco 1985 model, but was published earlier. It cites DiFrancesco 1985 as "1984 (in the press)".

1985 DiFrancesco mPf

Base: McAllister 1975 | In PMR | Paper DiFrancesco, Noble (1985) A Model of the Cardiac Electrical Activity Incorporating Ionic Pumps and Concentration Changes

Known as: DiFrancesco-Noble model

Bits:

  • INaK new formulation

1985 Reiner RSf

Base: Bristow 1982 | Paper Reiner, Antzelevitch (1985) Phase resetting and annihilation in a mathematical model of sinus node

Known as: Reiner-Antzelevitch

1987 Drouhard mV

Base: Beeler 1977 | In PMR | Paper Drouhard, Roberge (1987) Revised formulation of the Hodgkin-Huxley representation of the sodium current in cardiac cells

Known as: Drouhard-Roberge, BRDR

Modifications:

  • Remove INa j gate again

1987 Hilgemann RAf

Base: DiFrancesco 1985 | In PMR | Paper Hilgemann, Noble (1987) Excitation-contraction coupling and extracellular calcium transients in rabbit atrium; reconstruction of basic cellular mechanisms

1987 Murphey RSf

Chapter: Murphey, Clark (1987) Parasympathetic control of the SA node cell in rabbit heart; a model. In: Activation, Metabolism and Perfusion of the Heart, eds Sideman, Beyar

1989 Noble mS

Base: Noble 1984 | In PMR | Chapter: "DiFrancesco, Noble, Denyer (1989) Ionic Mechanisms in Normal and Abnormal Cardiac Pacemaker Activity", in "Jacklet (Ed, 1989) Neuronal and Cellular Oscillators".

Known as: Noble-DiFrancesco-Denyer

1981 Fischmeister FPf

Base: McAllister 1975 | Abstract Fischmeister, Vassort (1981) The electrogenic NaCa exchange and the cardiac electrical activity; I Simulation on Purkinje fibre action potential

Abstract only.

1990 Earm RA

Base: Hilgemann 1987 | Code for this paper is inside "Oxsoft Heart" | In PMR | Paper Earm, Noble (1990) A model of the single atrial cell; relation between calcium current and calcium release

1990a Rasmusson FS

Base: DiFrancesco 1985, but mostly new | Paper Rasmusson, Clark et al., Campbell (1990) A mathematical model of a bullfrog cardiac pacemaker cell

Novelties:

  • Single cell data, improved modelling of extracellular cleft
  • Calcium buffering

1990b Rasmusson FA

Base: Rasmusson 1990a | Paper Rasmusson, Clark et al., Campbell (1990) A mathematical model of electrophysiological activity in a bullfrog atrial cell

1991 Luo GV

Base: Beeler 1977 | Updated matlab code | In PMR | Paper Luo, Rudy (1991) A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction.

Known as: Luo-Rudy model, LR1, Luo-Rudy phase 1 model

Bits:

  • INa based on Ebihara 1980, but with a j gate added back in

1991 Noble GV

Base: Earm 1990 | Code for this paper is inside "Oxsoft Heart" | In PMR | Paper Noble, Noble et al., So (1991) The Role of Sodium-Calcium Exchange During the Cardiac Action Potential

1991 Wilders mS

Base: Noble 1984 | Paper Wilders, Jongsma, Van Ginneken (1991) Pacemaker activity of the rabbit sinoatrial node; A comparison of mathematical models

1993 Nordin GV

Base: DiFrancesco 1985 | Paper Nordin (1993) Computer model of membrane current and intracellular Ca2 flux in the isolated guinea pig ventricular myocyte Has erratum

Bits:

  • INaK new formulation

1994 Demir RS

Base: Rasmusson 1990 | In PMR | [Paper](Demir, Clark, Murphey, Giles (1994) A mathematical model of a rabbit sinoatrial node cell)

1994 Luo GV

Base: Luo 1991 | In PMR (with issues) | Paper Luo, Rudy (1994) A dynamic model of the cardiac ventricular action potential I; Simulations of ionic currents and concentration changes

Known as: LRd, LR2, Luo-Rudy phase 2 model

Modifications:

  • INaK new formulation
  • Rescaled gK1
  • ...
  • CICR

1995 Zeng GV

Base: 1994 Luo GV | In PMR (with issues) | Paper Zeng, Laurita, Rosenbaum, Rudy (1995) Two Components of the Delayed Rectifier K Current in Ventricular Myocytes of the Guinea Pig Type

Modifications:

  • Splits IK into IKr and IKs
  • Calcium buffering, with an analytical solution to a higher-order problem that ends up involving arccos and cos.
  • ...

1996a Dokos RS

Base: Noble 1989, Wilders 1991 | In PMR | Paper Dokos, Celler, Lovell (1996) Ion Currents Underlying Sinoatrial Node Pacemaker Activity; A New Single Cell Mathematical Model

1996b Dokos RS

Base: Dokos 1996a | Paper Dokos, Celler, Lovell (1996) Vagal Control of Sinoatrial Rhythm; a Mathematical Model

Modifications:

  • Contains ACh storage and interaction

1996 Lindblad RA

Base: Demir 1994 | In PMR | Paper Lindblad, Murphey, Clark Giles (1996) A model of the action potential and underlying membrane currents in a rabbit atrial cell

1997 Shaw GV

Base: Zeng 1995 | In PMR | Paper Shaw, Rudy (1997) Electrophysiologic effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration

1998 Courtemanche HA

Base: Luo 1994 | In PMR | In Myokit repo | Paper Courtemanche, Ramirez, Nattel (1998) Ionic mechanisms underlying human atrial action potential properties; insights from a mathematical model

1998 Jafri GV

Base: Luo 1994 | In PMR | Paper Jafri, Rice, Winslow (1998) Cardiac Ca2 Dynamics; The Roles of Ryanodine Receptor Adaptation and Sarcoplasmic Reticulum Load

Modifications:

  • Elements of Keizer & Levine 1996 Ca-induced Ca release model

1998 Noble GV

Base: Noble 1991 | Code for this paper is inside "Oxsoft Heart" | Official CellML (in PMR) | Paper (not online) Noble, Varghese, Kohl, Noble (1998) Improved guinea-pig ventricular cell model incorporating a diadic space, IKr and IKs, and length- and tension-dependent processes | Correction (not online)

1998 Nygren HA

Base: Lindblad 1996 | In Myokit repo | In PMR | Paper Nygren, Fiset et al., Giles (1998) Mathematical model of an adult human atrial cell; the role of K-currents in repolarization

1998 Priebe HV

Base: Luo 1994 | In Myokit repo | In PMR | Paper Priebe, Beuckelmann (1998) Simulation study of cellular electric properties in heart failure

1998 Riemer GV

Base: Luo 1994 | In PMR | Paper Riemer, Sobie, Tung (1998) Stretch-induced changes in arrhythmogenesis and excitability in experimentally based heart cell models

Modifications:

  • Added stretch channel

1999 Chudin GV

Base: Zeng 1995 | Paper Chudin, Goldhaber et al., Kogan (1999) Intracellular Ca dynamics and the stability of ventricular tachycardia

Modifications:

  • New calcium handling

1999 Clancy GV

Base: Zeng 1995 | Paper Clancy, Rudy (1999) Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia

Modifications:

  • New (baseline and mutated) INa model

1999 Demir RS

Base: Demir 1994 | In PMR | Paper Demir, Clark, Giles (1999) Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart; a unifying model

Modifications:

  • Added cAMP and ACh response

1999 Dumaine GV

Base: Luo 1994 | In PMR | Paper Dumaine, Towbin et al., Antzelevitch (1999) Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent

1999 Viswanathan GV

Base: Zeng 1995 | In PMR | Paper Viswanathan, Shaw, Rudy (1999) Effects of IKr and IKs Heterogeneity on Action Potential Duration and Its Rate Dependence; A Simulation Study

1999 Winslow CV

Base: Jafri 1998 | In PMR | Paper Winslow, Rice et al., O'Rourke (1999) Mechanisms of Altered Excitation-Contraction Coupling in Canine Tachycardia-Induced Heart Failure, II Model Studies

2000 Endresen RS

Base: Rederive everything | Paper Endresen, Hall, Hoye, Myrheim (2000) A theory for the membrane potential of living cells

Novelties:

  • The paper contains nice derivations of e.g. gating and transport equations
  • The paper uses an analytical V equation

2000 Faber GV

Base: Viswanathan 1999 | Original C++ code | In PMR | Paper Faber, Rudy (2000) Action Potential and Contractility in [Na+]i Overloaded Cardiac Myocytes

2000 Greenstein CV

Base: Winslow 1999 | In PMR | Paper Greenstein, Wu et al., Winslow (2000) Role of the calcium-independent transient outward current Ito1 in shaping action potential morphology and duration

2000 Ramirez CA

Base: Courtemanche 1998 | In PMR (with issues) | Paper Ramirez, Nattel, Courtemanche (2000) Mathematical analysis of canine atrial action potentials; rate, regional factors, and electrical remodeling

2000 Rice GV

Base: Jafri 1998 | In PMR | Paper Rice, Jafri, Winslow (2000) Modeling short-term interval-force relations in cardiac muscle

2000 Zhang RS

Base: Mostly new? | In PMR | Paper Zhang, Holden et al., Boyett (2000) Mathematical models of action potentials in the periphery and center of the rabbit sinoatrial node

2001 Boyett RS

Base: Zhang 2000 | In PMR; with issues | Paper Boyett, Zhang, Garny, Holden (2001) Control of the pacemaker activity of the sinoatrial node by intracellular Ca; Experiments and modelling

2001 Hund GV

Base: Faber 2000 | Paper Hund, Kucera, Otani, Rudy (2001) Ionic Charge Conservation and Long-Term Steady State in the Luo-Rudy Dynamic Cell Model

Modifications:

  • Algebraic V (usually not inherited by next models!)
  • Stimulus current assigned to K+ in concentration updates

2001 Mazhari CV

Base: Winslow 1999 | In PMR | Paper Mazhari, Greenstein et al., Nuss (2001) Molecular interactions between two long-QT syndrome gene products, HERG and KCNE2, rationalized by in vitro and in silico analysis

2001 Michailova CV

Base: Winslow 1999 | In PMR | Paper Michailova, McCulloch (2001) Model Study of ATP and ADP Buffering, Transport of Ca2 and Mg2, and Regulation of Ion Pumps in Ventricular Myocyte

2001 Noble GP

Base: Noble 1998 | In PMR | Paper not online: Noble, Noble (2001) Remodelling of calcium dynamics in guinea-pig ventricular cells

2001 Pandit LV

Base: Demir 1999, Winslow 1999 | In PMR | Paper Pandit, Clark, Giles, Demir (2001) A Mathematical Model of Action Potential Heterogeneity in Adult Rat Left Ventricular Myocytes

2001 Puglisi GV

Base: Luo 1994 | In PMR | Paper Puglisi, Bers (2001) LabHEART; an interactive computer model of rabbit ventricular myocyte ion channels and Ca transport

Known as: Puglisi-Bers, LabHEART

Modifications:

  • Rescaled gK1
  • ... see Table 1

2002 Clancy GV

Base: Clancy 1999, Viswanathan 1999 | In PMR | Paper Clancy, Rudy (1999) Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia

Modifications:

  • New (baseline and mutated) INa model

2002 Fox CV

Base: Chudin 1999 | In PMR | Paper Fox, McHarg, Gilmour (2002) Ionic mechanism of electrical alternans

2002 Kneller CA

Base: Ramirez 2000 | In PMR | Paper Kneller, Ramirez et al., Nattel (2002) Time-dependent transients in an ionically based mathematical model of the canine atrial action potential

2002 Kurata RS

Base: Wilders 1991, Demir 1994, Dokos 1996, Zhang 2000 | In PMR | Paper Kurata, Hisatome, Imanishi, Shibamoto (2002) Dynamical description of sinoatrial node pacemaking; improved mathematical model for primary pacemaker cell

2003 Cabo CV

Base: Luo 1994 | Paper Cabo, Boyden (2003) Electrical remodeling of the epicardial border zone in the canine infracted heart; a computational analysis

2003 Matsuoka GV

Base: Luo 1991, but lots of new things | Original Delphi code | Reimplementation in simBio | Official CellML (in PMR) | Paper Matsuoka, Sarai et al., Noma (2003) Role of individual ionic current systems in ventricular cells hypothesized by a model study

Known as: Kyoto model

Bits:

  • Contraction from Negroni 1996
  • INaK novel reduced formulation, based on INaCa
  • ...

2003 Pandit LV

Base: Pandit 2001 | In PMR | Paper Pandit, Giles, Demir (2003) A Mathematical Model of the Electrophysiological Alterations in Rat Ventricular Myocytes in Type-I Diabetes

2003 Sarai mS

Base: Matsuoka 2003 | Original Delphi code | Reimplementation in simBio | Official CellML (in PMR) | Paper Sarai, Matsuoka et al., Noma (2003) Role of individual ionic current systems in the SA node hypothesized by a model study

Based mostly on Rabbit and Guinea pig data. The Delphi and C++ code for this model is the same as that for Matsuoka 2003, but it has a mode switch.

2003 Saucerman LV

Base: Puglisi 2001 | Original matlab code | In PMR | Paper Saucerman, Brunton, Michailova, McCulloc (2003) Modeling beta-adrenergic control of cardiac myocyte contractility in silico

2003 Solovyova GV

Base: Noble 1998 | Paper Solovyova, Vikulova et al., Noble (2003) Mechanical interaction of heterogeneous cardiac muscle segments in silico; effects on Ca handling and action potential

Known as: Ekaterinburg-Oxford (EO) model

2004 Bassani-Altamirano mV

Base: Puglisi 2001 | Paper Bassani*, Altamirano*, Puglisi, Bers (2004) Action potential duration determines sarcoplasmic reticulum Ca reloading in mammalian ventricular myocytes (*contributed equally)

Note: Ferret, rabbit, and rat.

2004 Bondarenko MV

Base: Luo 1994, but many new formulations | In PMR | Paper Bondarenko, Szigeti et al., Rasmusson (2004) Computer model of action potential of mouse ventricular myocytes

2004 Hund CV

Base: Hund 2001 (arguably, most of the formulations are new, but the supplement is written in a way that strongly suggests this model was based on LRd2). | Updated matlab and C++ code | In PMR | Paper Hund, Rudy (2004) Rate Dependence and Regulation of Action Potential and Calcium Transient in a Canine Cardiac Ventricular Cell Model

Known as: HRd

Bits:

  • CaMKII from Hanson et al 1994
  • INaCa from Weber et al 2001
  • INa from Luo 1994
  • INaL from Luo 1994 and Maltsev et al 2001
  • Cl regulation from Baumgarten et al [28]
  • Iup, Ileak, Itr from Luo 1994
  • INaK, IKp, IK1, IpCa from Luo 1994

2004 Iyer HV

Base: Winslow 1999 and others | In Myokit repo | In PMR | Paper Iyer, Mazhari, Winslow (2004) A computational model of the human left-ventricular epicardial myocyte

Known as: Iyer-Mazhari-Winslow

2004 Katsnelson RV

Base: Solovyova 2003 | Paper Katsnelson, Nikitina et al., Markhasin (2004) Influence of viscosity on myocardium mechanical activity; a mathematical model

2004 Matsuoka GV

Base: Matsuoka 2003 | Reimplementation in simBio | Paper Matsuoka, Sarai, Jo, Noma (2004) Simulation of ATP metabolism in cardiac excitation-contraction coupling

Modifications:

  • Added mitochondrial model

2004 Saucerman LV

Base: Saucerman 2003 | Original matlab code | Paper Saucerman, McCulloch (2004) Mechanistic systems models of cell signaling networks; a case study of myocyte adrenergic regulation

2004 Saucerman RV

Base: Puglisi 2001 | Original matlab code | Paper Saucerman, Healy et al., McCulloch (2004) Proarrhythmic consequences of a KCNQ1 AKAP-binding domain mutation; computational models of whole cells and heterogeneous tissue

2004 Shannon RV

Base: Puglisi 2001 | Original C code | Grandi's matlab | Another matlab | In PMR | Paper Shannon, Wang et al., Bers (2004) A mathematical treatment of integrated Ca dynamics within the ventricular myocyte

Known as: Chicago model

Modifications:

  • Rescaled gK1
  • ...

2004 Ten Tusscher HV

Base: Mostly new? | Original C code | In Myokit repo | In PMR | Paper Ten Tusscher, Noble, Noble, Panfilov (2004) A Model for Human Ventricular Tissue

Known as: TNNP 2004

Bits:

  • INa with 3 gates, ref given to Beeler 1977
  • ICaL adapted from Luo 1994
  • INaK adapted from DiFrancesco 1985

2005 Krogh-Madsen Cdf

Base: Mostly new? | Paper Krogh-Madsen, Schaffer et al., Guevara (2005) An ionic model for rhythmic activity in small clusters of embryonic chick ventricular cells

2005 Kurata HV

Base: Priebe 1998 | Original simBio code | Matlab code by Kunichika Tsumoto | Paper Kurata, Hisatome, Matsuda, Shibamoto (2005) Dynamical Mechanisms of Pacemaker Generation in IK1-Downregulated Human Ventricular Myocytes; Insights from Bifurcation Analyses of a Mathematical Model

2005 Michailova CV

Base: Michailova 2001 | In PMR | Paper Michailova, Saucerman, Belik, McCulloch (2005) Modeling Regulation of Cardiac KATP and L-type Ca2 Currents by ATP, ADP, and Mg2

2006 Cortassa GV

Base: Rice 2000

Modifications:

  • Cortassa 2003 metabolism model

2006 Greenstein CV

Base: Greenstein 2000 (via Greenstein 2002 local control model) | Paper Greenstein, Hinch, Winslow (2006) Mechanisms of Excitation-Contraction Coupling in an Integrative Model of the Cardiac Ventricular Myocyte

Modifications:

  • Ensemble behaviour of CaRUs using Hinch 2004 approximation

2006 Iribe GV

Base: Noble 1998 | In PMR | Paper Iribe, Kohl, Noble (2006) Modulatory effect of calmodulin-dependent kinase II (CaMKII) on sarcoplasmic reticulum Ca2 handling and interval-force relations; a modelling study

Modification:

  • Added Rice 1999 mechanics

2006 Mangoni MS

Base: Zhang 2000 | Paper Mangoni, Traboulsie et al., Lory (2006) Bradycardia and Slowing of the Atrioventricular Conduction in Mice Lacking CaV31 alpha-1g T-Type Calcium Channels

2006 Pasek LV

Base: Pandit 2001 | In PMR | Paper Pasek, Simurda, Christe (2006) The functional role of cardiac T-tubules explored in a model of rat ventricular myocytes

Modifications:

  • Inclusion of a restricted "tubular" space.

2006 Sato CV

Base: Fox 2002 | Paper Sato, Shiferaw et al., Karma (2006) Spatially Discordant Alternans in Cardiac Tissue; Role of Calcium Cycling

2006 Ten Tusscher HV

Base: Ten Tusscher 2004 | Original C code | In Myokit repo | In PMR | Paper Ten Tusscher, Panfilov (2006) Alternans and spiral breakup in a human ventricular tissue model

Known as: TP 2006

Modifications:

  • Added dyadic subspace
  • Changed IKr conductance
  • Changed IKs conductance and rates
  • Changed ICaL conductance and rates, added gate
  • Changed INaK conductance
  • Changed IpCa conductance
  • New Irel formulation
  • Changed Ileak and Iup rate
  • Added transfer equations for new subspace

2006 Takeuchi GV

Base: Terashima 2006 | Original simBio code | Paper Takeuchi, Tatsumi et al., Noma (2006) Ionic Mechanisms of Cardiac Cell Swelling Induced by Blocking NaK Pump As Revealed by Experiments and Simulation

2006 Terashima GV

Base: Matsuoka 2004 | Original simBio code | Paper Terashima, Takeuchi et al., Noma (2006) Modelling Cl homeostasis and volume regulation of the cardiac cell

Modifications:

  • Chloride dynamics
  • Cell volume dynamics

2007 Faber GV

Base: Hund 2001 |Original matlab and C++ code | Paper Faber, Silva, Livshitz, Rudy (2007) Kinetic Properties of the Cardiac L-Type Ca Channel and Its Role in Myocyte Electrophysiology; A Theoretical Investigation

Known as: Faber-Rudy

2007 Grandi RV

Base: Shannon 2004 | Paper Grandi, Puglisi et al., Bers (2007) Simulation of Ca-calmodulin-dependent protein kinase II on rabbit ventricular myocyte ion currents and action potentials

2007 Iyer HV

Base: Iyer 2004 | In PMR | Paper Iyer, Hajjar, Armoundas (2007) Mechanisms of Abnormal Calcium Homeostasis in Mutations Responsible for Catecholaminergic Polymorphic Ventricular Tachycardia

2007 Kuzumoto GV

Base: Takeuchi 2006 | Original simBio code | Paper Kuzumoto, Takeuchi et al., Matsuoka (2008) Simulation analysis of intracellular Na and Cl homeostasis during beta1-adrenergic stimulation of cardiac myocyte

Modifications:

  • Beta-adrenergic signalling
  • ...

2007 Livshitz CV

Base: Hund 2004 | Original matlab code | In Myokit repo | In PMR | Paper Livshitz, Rudy (2007) Regulation of Ca and electrical alternans in cardiac myocytes; role of CAMKII and repolarizing currents

2007 Niederer LV

Base: Pandit 2001 | In PMR | Paper Niederer, Smith (2007) A Mathematical Model of the Slow Force Response to Stretch in Rat Ventricular Myocytes

Modifications:

  • Added Hinch Ca model
  • Added Niederer 2006 contraction

2007 Terkildsen GV

Base: Hund 2001 | Paper

Modifications:

  • INaK from Smith 2004, updated by same authors
  • IKATP from Michailova
  • Cell volume regulation and water flux
  • Metabolite concentrations

2008 Benson CV

Base: Hund 2004 | In PMR | Paper Benson, Aslanidi, Zhang, Holden (2008) The canine virtual ventricular wall; A platform for dissecting pharmacological effects on propagation and arrhythmogenesis

2008 Fink HV

Base: Ten Tusscher 2006 | In Myokit repo | In PMR | Paper Fink, Noble et al., Giles (2008) Contributions of HERG K current to repolarization of the human ventricular action potential

Modifications:

  • New IK1 formulation, based on Yan & Ishihara 2005
  • New IKr formulation
  • Rescaled IKs

2008 Himeno GS

Base: Sarai 2003, Kuzumoto 2007 | Original simBio code | Paper Himeno, Sarai, Matsuoka, Noma (2008) Ionic mechanisms underlying the positive chronotropy induced by beta1-adrenergic stimulation in guinea pig sinoatrial node cells

2008 Hund CV

Base: Livshitz 2007 | Original C++ code

2008 Korhonen Md

Base: Dokos 1996, Bondarenko 2004 | Paper Korhonen, Rapila, Tavi (2008) Mathematical model of mouse embryonic cardiomyocyte excitation-contraction coupling

2008 Kurata RS

Base: Kurata 2002 | Paper Kurata, Matsuda, Hisatome, Shibamoto (2008) Regional difference in dynamical property of sinoatrial node pacemaking; role of Na channel current

2008 Mahajan-Shiferaw RV

Base: Shannon 2004 | In PMR | Paper Mahajan*, Shiferaw* et al., Weiss (2008) A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates

2008 Pasek GV

Base: Hund 2001 with many changes | In PMR | Paper Pasek, Simurda, Orchard, Christe (2008) A model of the guinea-pig ventricular cardiac myocyte incorporating a transverse-axial tubular system

2008 Ten Tusscher HP

Base: Ten Tusscher 2006 | Paper Ten Tusscher, Panfilov (2008) Modelling of the ventricular conduction system

Modifications:

  • Scaled GKs by 0.35, GNa by 2.94. No other changes.

2008 Terkildsen LV

Base: Pandit 2001 | Original CellML (in PMR) | Paper Terkildsen, Niederer et al., Smith (2008) Using Physiome standards to couple cellular functions for rat cardiac excitation-contraction

Known as: PHN

Modifications:

  • Niederer 2006 contraction model
  • Hinch calcium dynamics

2008 Saucerman RV

Base: Shannon 2004 | Original matlab code | In PMR | Paper Saucerman, Bers (2008) Calmodulin mediates differential sensitivity of CaMKII and calcineurin to local Ca2 in cardiac myocytes

2008 Sulman GV

Base: Solovyova 2003 | In PMR | Paper Sulman, Katsnelson, Solovyova, Markhasin (2008) Mathematical modeling of mechanically modulated rhythm disturbances in homogeneous and heterogeneous myocardium with attenuated activity of Na-K pump

2008 Wang Md

Base: Bondarenko 2004 | In PMR | Paper Wang, Sobie (2008) Mathematical model of the neonatal mouse ventricular action potential

2009a Aslanidi RA

Base: Lindblad 1996 | In PMR (with help from original authors) | Paper Aslanidi, Boyett et al., Zhang (2009) Mechanisms of transition from normal to reentrant electrical activity in a model of rabbit atrial tissue; interaction of tissue heterogeneity and anisotropy

2009b Aslanidi CP

Base: Benson 2008 | In PMR (with help from original authors) | Paper Aslanidi, Stewart, Boyett, Zhang (2009) Optimal Velocity and Safety of Discontinuous Conduction through the Heterogeneous Purkinje-Ventricular Junction

2009 Decker CV

Base: Hund 2008 | Original matlab and C++ code | In Myokit repo | In PMR | Paper Decker, Heijman et al., Rudy (2009) Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium

2009 Grandi HV

Base: Ten Tusscher 2004 | Paper Grandi, Pasqualini et al., Severi (2009) Theoretical investigation of action potential duration dependence on extracellular Ca in human cardiomyocytes

2009 Inada mN

Base: Lindblad 1996, Kurata 2002 | In PMR | Paper Inada, Hancox, Zhang, Boyett (2009) One-Dimensional Mathematical Model of the Atrioventricular Node Including Atrio-Nodal, Nodal, and Nodal-His Cells

2009 Korhonen Ld

Base: Pandit 2001, Bondarenko 2004 | Paper Korhonen, Hanninen, Tavi (2009) Model of excitation-contraction coupling of rat neonatal ventricular myocytes

2009 Koivumaki MV

Base: Bondarenko 2004 | Paper Koivumaki, Korhonen et al., Tavi (2009) Regulation of excitation-contraction coupling in mouse cardiac myocytes; integrative analysis with mathematical modelling

2009 Livshitz GV

Base: Faber 2007 | Original matlab code | Paper Livshitz, Rudy (2009) Uniqueness and Stability of Action Potential Models during Rest, Pacing, and Conduction Using Problem-Solving Environment

2009 Livshitz CV

Base: Hund 2004 | Original matlab code | Paper Livshitz, Rudy (2009) Uniqueness and Stability of Action Potential Models during Rest, Pacing, and Conduction Using Problem-Solving Environment

2009 Maleckar HA

Base: Nygren 1998 | In Myokit repo | In PMR | Paper Maleckar, Greenstein, Giles, Trayanova (2009) K current changes account for the rate dependence of the action potential in the human atrial myocyte

2009 Maltsev RS

Base: Kurata 2002, Shannon 2004 | In PMR | Paper Maltsev, Lakatta (2009) Synergism of coupled subsarcolemmal Ca2 clocks and sarcolemmal voltage clocks confers robust and flexible pacemaker function in a novel pacemaker cell model

2009 Stewart HP

Base: Ten Tusscher 2006 | Original CellML code (in PMR) | In Myokit repo | Paper Stewart, Aslanidi et al., Zhang (2009) Mathematical model of the electrical action potential of Purkinje fibre cells

2010 Grandi HV

Base: Shannon 2004 | Original matlab code | In Myokit repo | In PMR | Paper Grandi, Pasqualini, Bers (2010) A novel computational model of the human ventricular action potential and Ca transient

Known as: Grandi-Pasqualini-Bers human ventricular model, GPB

Note: Also credited as 2009 due to publication date being listed as 2009 and date of issue it appeared in listed as 2010.

Modifications:

  • Scaled gK1
  • ...

2010 Imtiaz RS

Base: Kurata 2002 | Paper Imtiaz, von der Weid, Laver, van Helden (2010) SR Ca store refill; a key factor in cardiac pacemaking

2010 Korhonen Md

Base: Korhonen 2008 | Paper Korhonen, Rapila et al., Tavi (2010) Local Ca releases enable rapid heart rates in developing cardiomyocytes

2010 Li MV

Base: Bondarenko 2004 | Official CellML (in PMR) | Paper Li, Niederer et al., Smith (2010) A mathematical model of the murine ventricular myocyte; a data-driven biophysically based approach applied to mice overexpressing the canine NCX isoform

2010 Maltsev RS

Base: Maltsev 2009 | Paper Maltsev, Lakatta (2010) A novel quantitative explanation for the autonomic modulation of cardiac pacemaker cell automaticity via a dynamic system of sarcolemmal and intracellular proteins

2010 Sampson-Iyer HP

Base: Iyer 2004 | Original fortran code | In Myokit repo | In PMR | Paper Sampson, Iyer, Marks, Kass (2010). A computational model of Purkinje fibre single cell electrophysiology: implications for the long QT syndrome

2010 Soltis RV

Base: Saucerman 2008 | Original matlab code | Paper Soltis, Saucerman (2010) Synergy between CaMKII Substrates and beta-Adrenergic Signaling in Regulation of Cardiac Myocyte Ca2+ Handling

2011 Carro HV

Base: Grandi 2010 | Official CellML (in PMR) | In Myokit repo | Paper Carro, Rodriguez, Laguna, Pueyo (2011) A human ventricular cell model for investigation of cardiac arrhythmias under hyperkalaemic conditions

Known as: CRLP

2011 Corrias RP

Base: DiFrancesco 1985, but many new parts | Official CellML (in PMR) | Paper Corrias, Giles, Rodriguez (2011) Ionic mechanisms of electrophysiological properties and repolarization abnormalities in rabbit Purkinje fibers

2011 Grandi-Pandit-Voigt HA

Base: Grandi 2010 | Original matlab code | In Myokit repo | In PMR | Paper Grandi*, Pandit*, Voigt* et al., Bers (2011) Human atrial action potential and Ca model; sinus rhythm and chronic atrial fibrillation (*shared first authorship)

Modifications:

  • Scaled gK1
  • ...

2011 Heijman CV

Base: Decker 2009 | Original matlab code | In Myokit repo | In PMR | Paper Heijman, Volders, Westra, Rudy (2011) Local control of beta-adrenergic stimulation; effects on ventricular myocyte electrophysiology and Ca transient

2011 Kharche MS

Base: Zhang 2000, Kurata 2002 | Paper Kharche, Yu, Lei, Zhang (2011) A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases

2011 Koivumaki-Korhonen HA

Base: Nygren 1998 | In Myokit repo | In PMR | Paper Koivumaki, Korhonen, Tavi (2011) Impact of Sarcoplasmic Reticulum Calcium Release on Calcium Dynamics and Action Potential Morphology in Human Atrial Myocytes; A Computational Study

2011 Li CP

Base: Decker 2009 | Original C++ code | Paper Li, Rudy (2011) A model of canine purkinje cell electrophysiology and Ca2 cycling; rate dependence, triggered activity, and comparison to ventricular myocytes

Known as: PRd

2011 Moreno HV

Base: Ten Tusscher 2006 | Paper Moreno, Zhu et al., Clancy (2011) A computational model to predict the effects of class I anti-arrhythmic drugs on ventricular rhythms

Modifications:

  • New INa model (new WT and drug-bound)

2011 O'Hara HV

Base: Livshitz 2009 | Original matlab and C++ code | In Myokit repo | Paper O'Hara, Virag, Varro, Rudy (2011) Simulation of the Undiseased Human Cardiac Ventricular Action Potential; Model Formulation and Experimental Validation

Bits:

  • INaK from Smith 2004, with reparametrisation

2011 Tao LS

Base: Zhang 2000, Kurata 2002 | Paper Tao, Paterson, Smith (2011) A model of cellular cardiac-neural coupling that captures the sympathetic control of sinoatrial node excitability in normotensive and hypertensive rats

2012 Christel MS

Base: Mangoni 2006 | Paper Christel, Cardona et al., Lee (2012) Distinct localization and modulation of Cav12 and Cav13 L-type Ca channels in mouse sinoatrial node

2012 Davies CV

Base: Benson 2008 | Original matlab code | In PMR | Paper Davies, Mistry et al., Abi-gerges (2012) An in silico canine cardiac midmyocardial action potential duration model as a tool for early drug safety assessment

2012 Morotti RV

Base: Shannon 2004 | Original matlab code | Paper Morotti, Grandi et al., Bers (2012) Theoretical Study of L-type Ca2+ Current Inactivation Kinetics during Action Potential Repolarization and Early Afterdepolarizations

Modifications:

  • ICaL model adapted and modified from Mahajan-Shiferaw

2012 Paci He

Base: Grandi 2009 | Paper Paci, Sartiani et al., Severi (2012) Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes

2012 Severi RS

Base: Maltsev 2009 | Official CellML (in PMR) | Paper Severi, Fantini, Charawi, DiFrancesco (2012) An updated computational model of rabbit sinoatrial action potential to investigate the mechanisms of heart rate modulation

Known as: SDiF

2012 Yaniv RS

Base: Maltsev 2010 | Paper Yaniv, Spurgeon et al., Lakatta (2012) Crosstalk between mitochondrial and sarcoplasmic reticulum Ca cycling modulates cardiac pacemaker cell automaticity

2012 Yang HV

Base: O'Hara 2011 | Updated C++ code | Paper Yang, Clancy (2012) In silico Prediction of Sex-Based Differences in Human Susceptibility to Cardiac Ventricular Tachyarrhythmias

2012 Yang MV

Base: Bondarenko 2004 | Original matlab code | Paper Yang, Saucerman (2012) Phospholemman is a negative feed-forward regulator of Ca in beta-adrenergic signaling, accelerating beta-adrenergic inotropy

2013 Colman HA

Base: Courtemanche 1998 | Paper Colman, Aslanidi et al., Zhang (2013) Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria

2013 Paci Hi

Base: Paci 2012 | In Myokit repo | In PMR | Paper Paci, Hyttinen, Aalto-Setala, Severi (2013) Computational Models of Ventricular and Atrial-Like Human Induced Pluripotent Stem Cell Derived Cardiomyocytes

2013 Voigt-Heijman HA

Base: Grandi 2011 | In Myokit repo | In PMR | Paper Voigt, Heijman et al., Dobrev (2013) Impaired Na-dependent regulation of acetylcholine-activated inward-rectifier K current modulates AP rate dependence in cAF

Modifications:

  • Added IKAch (Kneller et al. 2002)
  • Replaced INa with Courtemanche 1998 one
  • Modified IK1 (changed gK1 and a)

2013a Yaniv RS

Base: Yaniv 2012 | Paper Yaniv, Sirenko et al., Lakatta (2013) New evidence for coupled clock regulation of the normal automaticity of sinoatrial nodal pacemaker cells; bradycardic effects of ivabradine are linked to suppression of intracellular Ca cycling

2013b Yaniv RS

Base: Maltsev 2009 | Paper Yaniv, Stern, Lakatta, Maltsev (2013) Mechanisms of beat-to-beat regulation of cardiac pacemaker cell function by Ca cycling dynamics

2014 Asakura HV

Base: Grandi 2010, CaRU reduction used by Greenstein 2006 | Original visual basic code | Paper Asakura, Cha et al., Noma (2014) EAD and DAD mechanisms analyzed by developing a new human ventricular cell model

Known as: HuVECI (this terminology starts with Himeno 2015)

Note: This and subsequent huvec models use an iterative procedure to implement calcium buffering, which makes it difficult to replicate in modelling frameworks.

Modifications:

  • Contraction from Negroni and Lascano, 2008
  • Hinch 2004 approximation for LCC-RyR coupling
  • INa and INaL: mode-switching causes fixed fractions INa and INaL "mode"
  • IK1 from Ishihara & Yan 2007 and Yan & Ishihara 2005
  • ...

2014 Bondarenko MV

Base: Bondarenko 2004 | Paper Bondarenko (2014) A compartmentalized mathematical model of the beta1-adrenergic signaling system in mouse ventricular myocytes

Modifications:

  • Adds extensive beta1-adrenergic signalling

2014 Chang HA

Base: Grandi 2011 | Original OpenCARP code | Paper Chang, Bayer, Trayanova (2014) Disrupted calcium release as a mechanism for atrial alternans associated with human atrial fibrillation

2014 Davies MA

Base: Bondarenko 2004 | Paper Davies, Jin et al., Lei (2014) Mkk4 is a negative regulator of the transforming growth factor beta 1 signaling associated with atrial remodeling and arrhythmogenesis with age

2014 Morotti MV

Base: Soltis 2010 | Original matlab code | Paper Morotti, Edwards et al., Grandi (2014) A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII

2014 Tong mV

Base: Faber 2000 | Official CellML (in PMR) | Paper Tong, Ghouri, Taggart (2014) Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials

2014 Yang MV

Base: Yang 2012 mouse | Original matlab code | Paper Yang, Polanowska-Grabowska et al., Saucerman (2014) PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to beta-adrenergic signaling

2015 Himeno HV

Base: Asakura 2014 | Original (HuVECII) visual basic code | Official C | Updated (HuVECIII, 2017) visual basic | Paper Himeno, Asakura et al., Noma (2015) A human ventricular myocyte model with a refined representation of excitation-contraction coupling

Known as: HuVEC, or HuVECII

2015 Negroni RV

Base: Shannon 2004, Soltis 2010 | Original matlab code | Paper Negroni, Morotti et al., Bers (2015) Beta-adrenergic effects on cardiac myofilaments and contraction in an integrated rabbit ventricular myocyte model

Bits:

  • New myofilament contraction
  • Currents, Ca-handling, Na-handling: Shannon 2004
  • CaMKII, PKA: Soltis 2010

2015 Paci Hi

Base: Paci 2013 | Paper Paci, Hyttinen, Rodriguez, Severi (2015) Human induced pluripotent stem cell-derived versus adult cardiomyocytes; an in silico electrophysiological study on ionic current block effects

2015 Schmidt HA

Base: Voigt-Heijman 2013 | Paper

Modifications:

  • Added K2p3.1 current

2015 Yaniv RS

Base: Probably Yaniv 2013a | Paper Yaniv, Ganesan et al., Lakatta (2015) Real-time relationship between PKA biochemical signal network dynamics and increased action potential firing rate in heart pacemaker cells

2016 Behar RS

Base: Yaniv 2015 | Paper Behar, Ganesan, Zhang, Yaniv (2016) The autonomic nervous system regulates the heart rate through cAMP-PKA dependent and independent coupled-clock pacemaker cell mechanisms

2016 Gattoni LV

Base: Pandit 2001 | Paper Gattoni, Roe et al., Smith (2016) The calcium-frequency response in the rat ventricular myocyte; an experimental and modelling study

Modifications:

  • Hinch 2004 Ca dynamics
  • Lewalle et al. 2014 INaK model (despite Smith as co-author?)

2016 Majumder RAd

Base: Korhonen 2009 | Paper Majumder et al., Pijnappels, Panfilov (2016) A Mathematical Model of Neonatal Rat Atrial Monolayers with Constitutively Active Acetylcholine-Mediated K Current

2016 Morotti HA

Base: Grandi 2011 | Original matlab code | Paper Morotti, McCulloch et al., Grandi (2016) Atrial-selective targeting of arrhythmogenic phase-3 earlyafterdepolarizations in human myocytes

Modifications:

  • Markov model of INa with drug block adapted from Grandi 2007 and Wagner 2009 & Moreno 2013

2016 Passini HV

Base: O'Hara 2011 | Paper Passini, Minchole et al. Bueno-Orovio (2016) Mechanisms of Pro-Arrhythmic Abnormalities in Ventricular Repolarisation and Anti-Arrhythmic Therapies in Human Hypertrophic Cardiomyopathy

Modifications:

  • Rescaled Ito
  • Changed concentrations
  • Constant EK
  • Shifted act/inact curves INa, INaL, IK1
  • Modified INa steady states

2016 Pohl HS

Base: Dokos 1996a | Paper Pohl, Wachter, Hatam, Leonhardt (2016) A computational model of a human single sinoatrial node cell

2016 Varela CA

Base: Ramirez 2000 | Official CellML (in PMR) | Paper Varela, Colman, Hancox, Aslanidi (2016) Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action

2017 Aguilar HA

Base: Courtemanche 1998 | In Myokit repo | Paper Aguilar, Feng et al., Nattel (2017) Rate-dependent role of IKur in human atrial repolarization and atrial fibrillation maintenance

Modifications:

  • New IKur formulation
  • IKACh from Kneller 2002

2017 Bartos RV

Base: Negroni 2015 | Original matlab code | Paper Bartos, Morotti et al., Bers (2017) Quantitative analysis of the Ca2+-dependent regulation of delayed rectifier K+ current IKs in rabbit ventricular myocytes

Bits:

  • New IKs with Ca regulation

2017 Behar MS

Base: Kharche 2011 | Paper Behar, Yaniv (2017) Age-related pacemaker deterioration is due to impaired intracellular and membrane mechanisms; insights from numerical modeling

2017 Colman HA

Base: Colman 2013 | Paper Colman, Ni et al., Zhang (2017) In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis

2017 Dutta HV

Base: Li 2017 | Original code | Official CellML (in PMR) | In Myokit repo | Paper Dutta, Chang et al., Li (2017) Optimization of an in-silico cardiac cell model for proarrhythmia risk assessment

Known as: ORd-cipa-v1

Modifications:

  • Rescaling of conductances to better predict drug effects

2017 Ellinwood HA

Base: Morotti 2016 | Original matlab code | In Myokit repo | Paper Ellinwood, Dobrev, Morotti, Grandi (2017) Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity Erratum

Modifications:

  • Markov model of IKur with drug block adapted from Zhou et al. (PLoS ONE 2012; e42295)

2017 Fabbri HS

Base: Severi 2012 | Official CellML | Physiome reproduction paper | In Myokit repo | In PMR | Paper Fabbri, Fantini, Wilders, Severi (2017) Computational analysis of the human sinus node action potential; model development and effects of mutations

Known as: FWS

2017 Li HV

Base: O'Hara 2011 | Paper Li, Dutta et al., Colatsky (2017) Improving the in silico assessment of proarrhythmia risk by combining hERG channel-drug binding kinetics and multichannel pharmacology Known as: IKr-dynamic ORd model, original IKr-dyn ORd model

Modifications:

  • New IKr model with drug trapping

2017 Ni HA

Base: Colman 2017 | In Myokit repo | In PMR | Paper Ni, Whittaker et al., Zhang (2017) Synergistic Anti-arrhythmic Effects in Human Atria with Combined Use of Sodium Blockers and Acacetin

Bits:

  • Calcium subspaces based on Koivumaki 2011

2017 Paci Hi

Base: Paci 2015 | Paper Paci, Passini et al., Rodriguez (2017) Phenotypic Variability in LQT3 Human induced pluripotent stem cell-derived cardiomyocytes and their response to antiarrhythmic pharmacologic therapy; an in silico approach

2017 Surdo MV

Base: Morotti 2014 | Original matlab code | Paper Surdo, Berrera et al., Zaccolo (2017) FRET biosensor uncovers cAMP nano-domains at beta-adrenergic targets that dictate precise tuning of cardiac contractility

Bits:

  • Myofilament contraction from Negroni 2015

2018 Bai HA

Base: Ten Tusscher 2006 | Official CellML (in PMR) | In Myokit repo | Paper Bai, Gladding et al., Zhao (2018) Ionic and cellular mechanisms underlying TBX5-PITX2 insufficiency-induced atrial fibrillation; Insights from mathematical models of human atrial cells

Known as: TPA

2018 Colman HA

Base: Courtemanche 1998, Nygren 1998, Chang 2014 | Original C++ code | Paper Colman, Saxena, Kettlewell, Workman (2018) Description of the Human Atrial Action Potential Derived From a Single, Congruent Data Source; Novel Computational Models for Integrated Experimental-Numerical Study of Atrial Arrhythmia Mechanisms

2018 Koivumaki Hi

Base: Korhonen 2010, Paci 2015 | Original matlab code | Paper Koivumaki, Naumenko et al., Tavi (2018) Structural Immaturity of Human iPSC-Derived Cardiomyocytes; In Silico Investigation of Effects on Function and Disease Modeling

2018 Paci Hi

Base: Paci 2017 | In Myokit repo | Paper Paci, Polonen et al., Hyttinen (2018) Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities

2019 Loewe HS

Base: Fabbri 2017 | Official CellML (in PMR) | In Myokit repo | Paper Loewe, Lutz et al., Severi (2019) Hypocalcemia-Induced Slowing of Human Sinus Node Pacemaking

2019 Kernik Hi

Base: Shannon 2004, Ten Tusscher 2004, Maltsev 2009 | In Myokit repo | In PMR | Paper Kernik, Morotti et al., Clancy (2019) A computational model of induced pluripotent stem‐cell derived cardiomyocytes incorporating experimental variability from multiple data sources

2019 Tomek HV

Base: O'Hara 2011 | Original Matlab and official CellML code | In PMR | Paper Tomek, Bueno-Orovio et al., Rodriguez (2019) Development, calibration, and validation of a novel human ventricular myocyte model in health, disease, and drug block

2020 Alghamdi LS

Base: Tao 2011 | Paper Alghamdi, Boyett, Hancox, Zhang (2020) Cardiac pacemaker dysfunction arising from different studies of ion channel remodeling in the aging rat heart

2020 Asfaw MA

Base: Bondarenko 2014 | Original fortran code | Paper Asfaw, Tyan, Glukhov, Bondarenko (2020) A compartmentalized mathematical model of mouse atrial myocytes

Modifications:

  • Converted from ventricular model

2020 Balakina-Vikulova HV

Base: Ten Tusscher 2006, Sulman 2008 | Paper Balakina-Vikulova, Panfilov, Solovyova, Katsnelson (2020) Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model

2020 Bartolucci HV

Base: Dutta 2017 | Original matlab code | Official CellML (in PMR) | In Myokit repo | Paper Bartolucci, Passini et al., Severi (2020) Simulation of the effects of extracellular calcium changes leads to a novel computational model of human ventricular action potential with a revised calcium handling

Known as: BPS2020

Modifications:

  • New ICaL formulation (from Passini 2012 CINC)
  • ...

2020 Paci Hi

Base: Paci 2018 | In Myokit repo | Paper Paci, Passini et al., Entcheva (2020) All-Optical Electrophysiology Refines Populations of In Silico Human iPSC-CMs for Drug Evaluation

2020 Sengul Ayan LV

Base: Jafri 1998 but mostly new | Paper Sengul Ayan, Sircan et al., Yaras (2020) Mathematical model of the ventricular action potential and effects of isoproterenol-induced cardiac hypertrophy in rats

Modifications:

  • 5 parameter reformulation of most currents

2020 Tomek HV

Base: Tomek 2019 | Original Matlab and official CellML code | In Myokit repo | Paper 1 Tomek, Bueno-Orovio et al., Rodriguez (2019) Development, calibration, and validation of a novel human ventricular myocyte model in health, disease, and drug block | Paper 2 Tomek, Bueno-Orovio, Rodriguez (2020) ToR-ORd-dynCl; an update of the ToR-ORd model of human ventricular cardiomyocyte with dynamic intracellular chloride Known as: ToR-ORd-dynCl

Modifications:

  • Chloride homeostasis

2020 Trovato HP

Base: O'Hara 2011, Li 2011 | Original Matlab and official CellML code | In Myokit repo | In PMR | Paper Trovato, Passini et al., Rodriguez (2020) Human Purkinje in silico model enables mechanistic investigations into automaticity and pro-arrhythmic abnormalities

Modifications:

  • INa from Passini 2016
  • ...

2021 Akwaboah Hi

Base: Kurata 2002 and Courtemanche 1998 | In Myokit repo | Paper Akwaboah, Tsevi et al., Deo (2021) An in silico hiPSC-Derived Cardiomyocyte Model Built With Genetic Algorithm

Modifications:

  • INa from Luo 1991, with partial reparameterisation
  • Ito from Grandi 2010, with partial reparametrisation
  • IKr from Kurata 2002, with partial reparametrisation
  • If from Stewart 2009, with partial reperametrisation
  • ICaL from Kurata 2002, with partial reparametrisation
  • IKs from Courtemanche 1998
  • IKur from Courtemanche 1998
  • INaK from Courtemanche 1998
  • INaCa from Courtemanche 1998
  • IKACh from Kurata 2002
  • IK1 from Grandi 2010
  • IbCa from Courtemanche 1998
  • IbNa from Courtemanche 1998
  • IpCa from Courtemanche 1998
  • Calcium handling from Kurata 2002

2021 Fogli Iseppe HV

Base: Yang 2012 | Original C++ code | Paper Fogli Iseppe, Ni et al., Grandi (2021) Sex-specific classification of drug-induced Torsade de Pointes susceptibility using cardiac simulations and machine learning

2021 Forouzandehmehr Hi

Base: Paci 2020, Rice 2008 | Original Matlab Code | Paper Forouzandehmehr, Koivumäki, Hyttinen, Paci (2021) A mathematical model of hiPSC cardiomyocytes electromechanics

Modifications:

  • A new passive force accounting for inotropic effects of non-cardiomyocytes components in EHTs.

2021 Gaur PV

Base: O'Hara 2011, but many new parts | Original openCARP code and official Myokit, and CellML code | Paper Gaur, Qi et al., Vigmond (2021) A computational model of pig ventricular cardiomyocyte electrophysiology and calcium handling; Translation from pig to human electrophysiology

2021 Hoekstra HS

Base: Fabbri 2017 | Paper Hoekstra, van Ginneken, Wilders, Verkerk (2021) HCN4 current during human sinoatrial node-like action potentials

2021 Margara HV

Base: O'Hara 2011 and Tomek 2020 | Paper Margara, Wang et al., Rodriguez (2021) In-silico human electro-mechanical ventricular modelling and simulation for drug-induced pro-arrhythmia and inotropic risk assessment

Modifications:

  • Added Land contraction model to O'Hara and Tomek, partially recalibrated and compared.

2021 Morotti HV

Base: Grandi 2010 | Original code | Paper Morotti, Liu et al., Grandi (2024) Quantitative cross-species translators of cardiac myocyte electrophysiology; Model training, experimental validation, and applications

Modifications:

  • Included (and adapted) PKA and CaMKII signaling from Soltis-Saucerman

2021 Morotti MS

Base: Kharche 2011 | Original matlab code | Paper Morotti, Ni et al., Grandi (2021) Intracellular Na+ Modulates Pacemaking Activity in Murine Sinoatrial Node Myocytes: An In Silico Analysis

2021 Morotti MV

Base: Surdo 2017 | Original code | Paper Morotti, Liu et al., Grandi (2024) Quantitative cross-species translators of cardiac myocyte electrophysiology; Model training, experimental validation, and applications

Modifications:

  • Updated PKA signaling
  • Improved implementation of ODE calculation

2021 Morotti RV

Base: Bartos 2017 | Original code | Paper Morotti, Liu et al., Grandi (2024) Quantitative cross-species translators of cardiac myocyte electrophysiology; Model training, experimental validation, and applications

Modifications:

  • Updated PKA signaling
  • Improved implementation of ODE calculation

2022 Bartolucci HV

Base: Bartoluci 2020 | Paper Bartolucci, Forouzandemehr, Severi, Paci (2022) A Novel In Silico Electromechanical Model of Human Ventricular Cardiomyocyte

Known as: BPSLand

Modifications:

  • Added Land 2017 contraction model
  • ...

2022 Doste HV

Base: Tomek 2020, Heijman 2011 | Original matlab code | Paper Doste, Coppini, Bueno-Orovio (2022) Remodelling of potassium currents underlies arrhythmic action potential prolongation under beta-adrenergic stimulation in hypertrophic cardiomyopathy

Modifications:

  • Added beta-adrenergic signalling

2022 Forouzandehmehr Hi

Base: Forouzandehmehr 2021, Tran 2017 | Original Matlab Code | Paper Forouzandehmehr, Paci, Koivumäki, Hyttinen (2022) Altered contractility in mutation-specific hypertrophic cardiomyopathy: A mechano-energetic in silico study with pharmacological insights

Modifications:

  • Offering mechanoenergetic parameter identification to model MYH7R403Q HCM+Mavacamten, and dose-dependent effects of Blebbistatin and Omecamtiv mecarbil.

2022 Kohjitani Hi

Base: Himeno 2015 | Code not quite available, point to e-Heart | Paper Kohjitani, Koda et al., Kimura (2022) Gradient-based parameter optimization method to determine membrane ionic current composition in human induced pluripotent stem cell-derived cardiomyocytes

2022 Moise RS

Base: Severi 2012 | Original matlab code | Paper Moise, Weinberg (2022) Emergent Electrical Activity, Tissue Heterogeneity, and Robustness in a Calcium Feedback Regulatory Model of the Sinoatrial Node

2023 Heijman HA

Base: Grandi 2011 | Original matlab code | Paper Heijman, Zhou et al., Dobrev (2023) Enhanced Ca-Dependent SK-Channel Gating and Membrane Trafficking in Human Atrial Fibrillation

2023 Herrera HA

Base: Ellinwood 2017 | Original matlab code | Paper Herrera, Zhang et al., Morotti (2023) Dual effects of the small-conductance Ca-activated K current on human atrial electrophysiology and Ca-driven arrhythmogenesis; an in silico study

Also cites a 2020 Ni paper, but that refers to Ellinwood.

2023 Mahzar HA

Base: Koivumaki 2011, Regazzoni 2020 | Paper Mazhar, Bartolucci et al., Severi (2023) A detailed mathematical model of the human atrial cardiomyocyte: integration of electrophysiology and cardiomechanics

Known as: MBS2023

2023 Ni HA

Base: Morotti 2017 | Original C++ code | Paper Ni, Morotti et al., Grandi (2023) Integrative human atrial modelling unravels interactive PKA and CaMKII signalling as key determinants of atrial arrhythmogenesis

2024 Botti Hi

Base: Paci 2020 | Original matlab code | Paper Botti, Bartolucci et al., Severi (2024) A novel ionic model for matured and paced atrial-like human iPSC-CMs integrating IKur and IKCa currents

Modifications:

  • Added IKur and IKCa
  • Rescaled parameters to match atrial data

2024 Forouzandehmehr Hi

Base: Forouzandehmehr, Tran 2009, Tran 2017 | Original Matlab Code | Paper Forouzandehmehr, Paci, Hyttinen, Koivumäki (2024) In silico study of the mechanisms of hypoxia and contractile dysfunction during ischemia and reperfusion of hiPSC cardiomyocytes

Modifications:

  • A new extracellular oxygen dynamics formulation, linking the cellular ionic and myofilament ATPase rate changes to extracellular and capillary level oxygen concentration.
  • Extending modeling approach to simulations of ischemia and Levosimendan mechanism of action.

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A list of (detailed, non-stochastic) action potential models, with links to papers, source code, CellML and Myokit implementations

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