Adult Rat Left Ventricular Myocyte Model, 2001
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
This CellML version of the model represents the epicardial cell. In addition to the formulation given by the paper and the author's later Corrections document, the IStim current has been adjusted to produce 1 Hz stimulations for 10 seconds.
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 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.
W
Giles
R
11720973
S
Demir
S
Biophysical Journal
Michael
Cooling
James
Lawson
Richard
A mathematical model of action potential heterogeneity in adult rat left ventricular myocytes
81 6
3029
3051
James
Lawson
Richard
S
Demir
S
Rat ventricular myocyte model from the original Pandit 2001 paper: epicardial cell
Department of Physiology, Anatomy & Genetics, University of Oxford
R
Clark
B
Oxford University
Department of Physiology, Anatomy & Genetics
keyword
electrophysiology
ventricular myocyte
cardiac
rat
penny.noble@dpag.ox.ac.uk
Michael
Cooling
Updated documentation image to full cell diagram.
2008-05-26T11:07:32+12:00
100000
0.001
This model has been curated by Penny Noble of Oxford University
Unknown Person
2001-12-00 00:00
Added some cmeta:id's to current and flux variables
Summary of code changes from v07:
1. The inward rectifying current (Ik1) had a 0.0001 term in the numerator which has been changed to 0.001 to match the paper and corrections document.
2. Mmax, hmax, jmax, dmax, f11max, f12max, Caactmax, rmax, smax sslowmax, rssmax and sssmax were all called minfinity, hinfinity, jinfinity, dinfinity...etc. These have been changed to ...max variables for consistency internally and with the paper.
3. The Ryanodine equations had odd dimensionless units and terms which divide by 1 to make the units work. Here variables 'n' and 'm' were removed and the units set as per the original model of Keizer, J. and Levine, L. Ryanodine receptor adaptation and Ca2+(-)induced Ca2+ release-dependent Ca2+ oscillations. Biophys. J. 71,6, 3477-3487 (1996). This was after discussion with both Catherine Lloyd and Penny Noble. The units are now correct.
4. Units millimolar_4 was misnamed and is now per_millimolar4.
5. Units nanoA_millimolar_4 was misnamed and is now nanoA_per_millimolar4.
6. Not a change but just to note that this implementation has a 1Hz stimulus for 10 seconds built in.
2007-01-16T00:00:00+00:00
James
Lawson
Richard
Several variables were given cmeta:id's to allow creation of a PCEnv session file.
2007-01-16T14:20:00+13:00
This version was created by Penny Noble of Oxford University and represents the EPICARDIAL CELL VARIANT. The model has been checked in COR.
2008-07-01T16:01:54+12:00
2007-06-22T14:17:56+12:00
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.
Catherine
Lloyd
May
S
Pandit
V
Penny
Noble
J
2008-07-31T10:37:18+12:00
A Mathematical Model of Action Potential Heterogeneity in Adult Rat Left Ventricular Myocytes
81
3029
3051
Mike
Cooling
Penny
Noble
J
11720973
2001-12-01 00:00
2008-06-13T13:56:13+12:00
Biophysical Journal
2007-11-01T12:18:01+13:00
W
Giles
R
Noticed the volumes for V_NSR and V_SS were wrong and have corrected them. They were wrong in version 7.
R
Clark
B
S
Pandit
V
2008-05-26T11:07:32+12:00