Adult Rat Left Ventricular Myocyte Model, 2001
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
This CellML version of the model represents the endocardial cell. The model has been checked in COR, OpenCell and JSim and it runs in all three to recreate the published results. The units have been checked and are consistent. Thank you to Frank Sachse for his helpful feedback and careful code checking.
Model Structure
ABSTRACT: Mathematical models were developed to reconstruct the action potentials (AP) recorded in epicardial and endocardial myocytes isolated from the adult rat left ventricle. The main goal was to obtain additional insight into the ionic mechanisms responsible for the transmural AP heterogeneity. The simulation results support the hypothesis that the smaller density and the slower reactivation kinetics of the Ca(2+)-independent transient outward K(+) current (I(t)) in the endocardial myocytes can account for the longer action potential duration (APD), and more prominent rate dependence in that cell type. The larger density of the Na(+) current (I(Na)) in the endocardial myocytes results in a faster upstroke (dV/dt(max)). This, in addition to the smaller magnitude of I(t), is responsible for the larger peak overshoot of the simulated endocardial AP. The prolonged APD in the endocardial cell also leads to an enhanced amplitude of the sustained K(+) current (I(ss)), and a larger influx of Ca(2+) ions via the L-type Ca(2+) current (I(CaL)). The latter results in an increased sarcoplasmic reticulum (SR) load, which is mainly responsible for the higher peak systolic value of the Ca(2+) transient [Ca(2+)](i), and the resultant increase in the Na(+)-Ca(2+) exchanger (I(NaCa)) activity, associated with the simulated endocardial AP. In combination, these calculations provide novel, quantitative insights into the repolarization process and its naturally occurring transmural variations in the rat left ventricle.
The complete original paper reference is cited below:
A Mathematical Model of Action Potential Heterogeneity in Adult Rat Left Ventricular Myocytes, Sandeep V. Pandit, Robert B. Clark, Wayne R. Giles and Semahat S. Demir, 2001,
Biophysical Journal
, 81, 3029-3051.
PubMed ID: 11720973
fluid compartment model of the rat epicardial/endocardial ventricular cell
A fluid compartment model of the rat epicardial/endocardial ventricular cell.
Simulation time domain
Universal gas constant
Potassium current through the hyperpolarization activated channel
Hyperpolarization activated channel potassium current
Potassium current through the hyperpolarization activated channel
Concentration of sodium in bulk cytosol
Simulation time domain
Concentration of potassium in bulk cytosol
Concentration of calcium in bulk cytosol
Voltage potential across the plasma membrane of the cardiomyocyte
Region of the sarcoplasmic reticulum connecting the junction sarcoplasmic reticulum regions
Network sarcoplasmic reticulum
Volume of matrix of network sarcoplasmic reticulum
Simulation time domain
Current through the steady-state outward potassium channel
Steady-state outward potassium channel current
Current through the steady-state outward potassium channel
Current through the transient outward potassium channel
Transient outward potassium channel current
Current through the transient outward potassium channel
Calcium concentration in the network regions of the sarcoplasmic reticulum
Temperature of the cardiac myocyte and its surrounding environment
Total portion of EGTA
Total concentration of EGTA in cytosol
Calcium concentration in the network regions of the sarcoplasmic reticulum
Concentration of potassium external to the cardiac myocyte
Nernst potential for sodium across the plasma membrane
Simulation time domain
Concentration of calcium in bulk cytosol
Concentration of calcium external to the cardiac myocyte
Voltage potential across the plasma membrane of the cardiomyocyte
Nernst potential for sodium across the plasma membrane
Current through the sodium/potassium pump
Sodium/potassium pump current
Current through the sodium/potassium pump
Current through the transient outward potassium channel
Current through the background potassium channel
Background potassium channel current
Current through the background potassium channel
Temperature of the cardiac myocyte and its surrounding environment
Concentration of potassium external to the cardiac myocyte
Universal gas constant
SR regions in close proximity to cytosolic diadic space
Junctional sarcoplasmic reticulum
Calcium flux from network SR into junctional SR by diffusion
Internal SR calcium transfer
Calcium flux between junctional and network sarcoplasmic reticulum
Space between t-tubule and junctional sarcoplasmic reticulum
Diadic space
Calcium concentration in diadic space
Concentration of calcium external to the cardiac myocyte
Nernst potential for sodium across the plasma membrane
Concentration of potassium in bulk cytosol
Total current through the hyperpolarization activated channel
Hyperpolarization activated channel current
Total current through the hyperpolarization activated channel
Voltage potential across the plasma membrane of the cardiomyocyte
Concentration of calcium external to the cardiac myocyte
Current through the background calcium channel
Background calcium channel current
Current through the background calcium channel
Voltage potential across the plasma membrane of the cardiomyocyte
Calcium bound to high affinity troponin C binding sites
Total portion of high affinity troponin C binding sites
Flux of troponin C high affinity binding of calcium
Troponin C high affinity binding site/calcium buffering
Binding of troponin C high affinity binding sites to calcium
Voltage potential across the plasma membrane of the cardiomyocyte
Faraday constant
Voltage potential across the plasma membrane of the cardiomyocyte
Simulation time domain
Potassium current through the hyperpolarization activated channel
Current through L-type calcium channel
L-type calcium channel current
Current through L-type calcium channel
Current through the steady-state outward potassium channel
Calcium concentration of fluid inside the junctional region of the sarcoplasmic reticulum
Voltage potential across the plasma membrane of the cardiomyocyte
Universal gas constant
Total portion of low affinity troponin C binding sites
Total concentration of low affinity troponin binding sites
Current through the background sodium channel
Background sodium channel current
Current through the background sodium channel
Concentration of potassium external to the cardiac myocyte
Voltage potential across the plasma membrane of the cardiomyocyte
Sodium current through the hyperpolarization activated channel
Hyperpolarization activated channel sodium current
Sodium current through the hyperpolarization activated channel
Concentration of calcium in bulk cytosol
Concentration of sodium external to the cardiac myocyte
Temperature of the cardiac myocyte and its surrounding environment
Calcium concentration in diadic space
Concentration of sodium external to the cardiac myocyte
Total current through the hyperpolarization activated channel
Calcium flux between junctional and network sarcoplasmic reticulum
Concentration of sodium in bulk cytosol
Simulation time domain
Volume of cytosol of the diadic space
Simulation time domain
Concentration of potassium in bulk cytosol
Total portion of calsequestrin
Total concentration of calmodulin in junctional sarcoplasmic reticulum
Nernst potential for sodium across the plasma membrane
Voltage potential across the plasma membrane of the cardiomyocyte
Calcium Flux from the cytosolic diadic space to the bulk cytosol by diffusion
Internal cytosolic calcium transfer
Calcium flux between the diadic subspace and blulk cytosol
Concentration of sodium in bulk cytosol
Current through the sodium/calcium exchanger
Sodium/calcium exchanger current
Current through the sodium/calcium exchanger
Catherine Lloyd
This version was created by Penny Noble of Oxford University and represents the EPICARDIAL CELL VARIANT. The model has been checked in COR, PCEnv and JSim and it runs in all three to recreate the published results. The units have been checked and are consistent. Thank you to Frank Sachse for his helpful feedback and careful code checking.
Several variables were given cmeta:id's to allow creation of a PCEnv session file.
Rat ventricular myocyte model from the original Pandit 2001 paper: endocardial cell
Department of Physiology, Anatomy & Genetics, University of Oxford
Added two differential equations to calculate HTRPNCa and LTRPNCa (the last two equations on page 3047 of the original paper). In doing so fixed the model to recreate the published results. Frank Sachse has checked this model in JSim and it also runs in this tool.
This model has been curated by Penny Noble of Oxford University
Oxford University
Department of Physiology, Anatomy & Genetics
Concentration of calcium bound to high affinity troponin C binding sites
Current through the inward rectifier potassium channel
Inward rectifier potassium channel current
Current through the inward rectifier potassium channel
Concentration of calcium in bulk cytosol
Concentration of sodium external to the cardiac myocyte
Universal gas constant
Voltage potential across the plasma membrane of the cardiomyocyte
Faraday constant
Volume of matrix of junctional sarcoplasmic reticulum
Calcium bound to low affinity troponin C binding site
Flux of troponin C low affinity binding of calcium
Troponin C low affinity binding site/calcium buffering
Binding of troponin C low affinity binding sites to calcium
Concentration of potassium external to the cardiac myocyte
Calcium concentration of fluid inside the junctional region of the sarcoplasmic reticulum
Calcium flux through the sarcoplasmic reticulum calcium pump (SERCA2a)
Sarcoplasmic reticulum calcium pump flux
Calcium flux through the sarcoplasmic reticulum calcium pump (SERCA2a)
Current through the background calcium channel
Temperature of the cardiac myocyte and its surrounding environment
Calcium flux through the sarcoplasmic reticulum calcium pump (SERCA2a)
Simulation time domain
Voltage potential across the plasma membrane of the cardiomyocyte
Simulation time domain
Voltage potential across the plasma membrane of the cardiomyocyte
Current through the sodium/calcium exchanger
Simulation time domain
Voltage potential across the plasma membrane of the cardiomyocyte
Universal gas constant
Universal gas constant
Voltage potential across the plasma membrane of the cardiomyocyte
Simulation time domain
James Lawson
This file contains a CellML description of Pandit et al.'s 2001 model of action potential heterogeneity in adult rat left ventricular myocytes. This variant describes the ENDOCARDIAL cell.
A mathematical model of action potential heterogeneity in adult rat left ventricular myocytes
81 6
Biophysical Journal
2001-12-01 00:00
keyword
electrophysiology
ventricular myocyte
cardiac
rat
Faraday constant
Calcium/troponin buffering
Flux of calcium binding to both low and high affinity sites on troponin C
Concentration of sodium external to the cardiac myocyte
Calcium concentration in diadic space
Concentration of calcium in bulk cytosol
Sodium current through the hyperpolarization activated channel
Simulation time domain
Voltage potential across the plasma membrane of the cardiomyocyte
Current through the sodium/calcium exchanger
Current through the inward rectifier potassium channel
Simulation time domain
Voltage potential across the plasma membrane of the cardiomyocyte
Temperature of the cardiac myocyte and its surrounding environment
Voltage potential across the plasma membrane of the cardiomyocyte
Total concentration of high affinity troponin binding sites
Volume of cytsol on cardiac myocyte
Concentration of calcium bound to low affinity troponin C binding sites
Faraday constant
Simulation time domain
Calcium concentration of fluid inside the junctional region of the sarcoplasmic reticulum
Current through the background sodium channel
Current through the inward rectifier potassium channel
Voltage potential across the plasma membrane of the cardiomyocyte
Nernst potential for sodium across the plasma membrane
Simulation time domain
Calcium concentration in diadic space
Current through the steady-state outward potassium channel
Calcium concentration in diadic space
Simulation time domain
Current through the transient outward potassium channel
Nernst potential for sodium across the plasma membrane
Nernst potential for sodium across the plasma membrane
Temperature of the cardiac myocyte and its surrounding environment
Faraday constant
Concentration of sodium in bulk cytosol
pandit_clark_giles_demir_2006_version06_variant01
Maxwell Neal
Rat cardiomyocyte electrophysiology and ion handling model (endocardial version)
pandit_clark_giles_demir_2006_version06_variant01
Simulation time domain
Simulation time domain
Current through the background potassium channel
Current through the sodium/potassium pump
Nernst potential for sodium across the plasma membrane
Voltage potential across the plasma membrane of the cardiomyocyte
Simulation time domain
Voltage potential across the plasma membrane of the cardiomyocyte
Current through the sarcolemmal calcium pump
Sarcolemmal calcium pump current
Current through the sarcolemmal calcium pump
Simulation time domain
Simulation time domain
Current through fast sodium channel
Fast sodium channel current
Current through fast sodium channel
Current through the sodium/potassium pump
Simulation time domain
Calcium flux between the diadic subspace and blulk cytosol
Current through fast sodium channel
Current through the sarcolemmal calcium pump
Calcium concentration in the network regions of the sarcoplasmic reticulum
Concentration of calcium in bulk cytosol
Simulation time domain
Current through the sarcolemmal calcium pump
Faraday constant
Simulation time domain
Calcium flux through sarcoplasmic reticulum RyR receptor
Sarcoplasmic reticulum calcium release flux
Calcium flux through sarcoplasmic reticulum RyR receptor
Flux of calcium binding to both low and high affinity sites on troponin C
Simulation time domain
Voltage potential across the plasma membrane of the cardiomyocyte
Current through L-type calcium channel
Voltage potential across the plasma membrane of the cardiomyocyte
Nernst potential of calcium across the plasma membrane
Simulation time domain
Faraday constant
Simulation time domain
Voltage potential across the plasma membrane of the cardiomyocyte
Current through L-type calcium channel
Calcium flux through sarcoplasmic reticulum RyR receptor
Current through fast sodium channel
Total portion of calmodulin
Total concentration of calmodulin in cytosol