Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This CellML version of the model has been checked in COR and OpenCell. A stimulus protocol has been added to allow the model to simulate action potentials for 5 seconds. The units are consistent and the model runs to recreate the published results. The parameter 'tissue' has been added to switch between the original (default value 0) and 'tissue' (any other value, for example 1) models.
Model Structure
ABSTRACT: BACKGROUND: Computational biology is a powerful tool for elucidating arrhythmogenic mechanisms at the cellular level, where complex interactions between ionic processes determine behavior. A novel theoretical model of the canine ventricular epicardial action potential and calcium cycling was developed and used to investigate ionic mechanisms underlying Ca2+ transient (CaT) and action potential duration (APD) rate dependence. METHODS AND RESULTS: The Ca2+/calmodulin-dependent protein kinase (CaMKII) regulatory pathway was integrated into the model, which included a novel Ca2+-release formulation, Ca2+ subspace, dynamic chloride handling, and formulations for major ion currents based on canine ventricular data. Decreasing pacing cycle length from 8000 to 300 ms shortened APD primarily because of I(Ca(L)) reduction, with additional contributions from I(to1), I(NaK), and late I(Na). CaT amplitude increased as cycle length decreased from 8000 to 500 ms. This positive rate-dependent property depended on CaMKII activity. CONCLUSIONS: CaMKII is an important determinant of the rate dependence of CaT but not of APD, which depends on ion-channel kinetics. The model of CaMKII regulation may serve as a paradigm for modeling effects of other regulatory pathways on cell function.
model diagram
Schematic diagram of the Hund and Rudy 2004 Canine Ventricular Cell Model.
The original paper reference is cited below:
Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model, Thomas J. Hund and Yoram Rudy, 2004,
Circulation,
110, 3168-3174. PubMed ID: 15505083
-Changed model cmeta:id, removed version
-added simulation metadata, model integrates for 5 seconds
10000
0.1
5000
Penny Noble
This CellML version of the model has been checked in COR. The units are consistent and the model runs to recreate the published results. The parameter 'tissue' has been added to switch between the original (default value 0) and 'tissue' (any other value, for example 1) models.
In the paper described here, Thomas Hund and Yoram Rudy present a detailed, and physiologically realistic, mathematical model of a canine ventricular cell. Model simulations are able to recreate the rate-dependent phenomena associated with ion-channel kinetics, action potential properties, and calcium ion handling. The model is based on an epicardial myocyte because these cells contain the largest transient outward potassium current (when compared with endocardial or midmyocardial myocytes). The calcium/calmodulin-dependent protein kinase (CaMKII) regulatory pathway was embedded within the electrophysiological model, incorporating calcium-release formulation, calcium subspace, and dynamic chloride handling. Results from the model simulations revealed CaMKII is an important determinant of the rate dependence of the calcium transient, but not of the action potential duration, which depends instead on the ion-channel kinetics.
10000
0.1
5000
University of Oxford
2008-06-18T01:17:05+12:00
Penny Noble
ventricular
myocyte
cardiac
carciac myocyte
cardiac electrophysiology
canine
electrophysiology
calcium
Yoram
Rudy
Thomas J
Hund
This CellML version of the model has been checked in COR. The units are consistent and the model runs to recreate the published results. The parameter 'tissue' has been added to switch between the original (default value 0) and 'tissue' (any other value, for example 1) models.
In the paper described here, Thomas Hund and Yoram Rudy present a detailed, and physiologically realistic, mathematical model of a canine ventricular cell. Model simulations are able to recreate the rate-dependent phenomena associated with ion-channel kinetics, action potential properties, and calcium ion handling. The model is based on an epicardial myocyte because these cells contain the largest transient outward potassium current (when compared with endocardial or midmyocardial myocytes). The calcium/calmodulin-dependent protein kinase (CaMKII) regulatory pathway was embedded within the electrophysiological model, incorporating calcium-release formulation, calcium subspace, and dynamic chloride handling. Results from the model simulations revealed CaMKII is an important determinant of the rate dependence of the calcium transient, but not of the action potential duration, which depends instead on the ion-channel kinetics.
Penny
Noble
2004-11-16 00:00
Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model (Basic Model)
Penny
Noble
2008-06-18T00:00:00+00:00
15505083
Circulation
penny.noble@dpag.ox.ac.uk
keyword
3168
110
3174
Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model
2008-06-18T11:54:20+12:00
This version of the model was created by literally translating to CellML from the original source code and then adding compartments and curating for unit consistency.
James
Lawson
Richard