The Most Recent Verison of the Luo-Rudy Mammalian Ventricular Model II
Catherine
Lloyd
Auckland Bioengineering Institute
Model Status
This model has been curated and is known to run in PCEnv and COR to recreate the published results. The units have been checked and are known to be consistent. The CellML model has been based on a translation of the LRd07 Matlab code which can be downloaded from the Rudy lab website. It is basically the Faber and Rudy 2000 model with the addition of a transient potassium current (Ito) and an updated Irel current.
Model Structure
A subsequent pair of papers by Ching-hsing Luo and Yoram Rudy (1994a; 1994b) further developed the Luo-Rudy I model by addressing some of the issues which were not investigated in their original model. In particular, the LR-II model incorporates a more thorough description of the processes which regulate intracellular calcium ion concentration and the movement of calcium ions through the cell and to and from the sarcoplasmic reticulum (see figure 1 below).
The complete original paper reference is cited below:
A Dynamic Model of the Cardiac Ventricular Action Potential - Simulations of Ionic Currents and Concentration Changes, Ching-hsing Luo and Yoram Rudy, 1994,
Circulation Research
, 74, 1071-1097.
Since the model was published in 1994, it has been updated several times, incorporating new experimental data taken from papers written by other authors. These modifications have been considered in the model presented here. To illustrate how the Luo-Rudy II dynamic model has been developed, see the sequence of diagrams. Please note that the 1997 Shaw and Rudy model diagram is identical to the 1999 Viswanathan model diagram since the only difference between the two models is that the Viswanathan model introduces a second activation gate (Xs2) into the formulation of IKs. In addition, the development of the Luo-Rudy II model has been documented by Yoram Rudy (To view this website, follow this link: http://rudylab.wustl.edu/research/cell/methodology/cellmodels/LRd/history.htm
cell diagram of the LR-II model showing ionic currents, pumps and exchangers within the sarcolemma and the sarcoplasmic reticulum
A schematic diagram describing the current flows across the cell membrane that are captured in the original, 1994 Luo-Rudy II, dynamic model.
cell diagram of the zeng model showing ionic currents, pumps and exchangers within the sarcolemma and the sarcoplasmic reticulum
A schematic diagram showing the updated Luo-Rudy II, dynamic model. In their 1995 ventricular model Zeng et al have included the slow and fast components of the delayed rectifier K+ current, IKr and IKs. A T-type Calcium channel (ICa(T)) is also added.
cell diagram of the shaw and viswanathan models showing ionic currents, pumps and exchangers within the sarcolemma and the sarcoplasmic reticulum
In their 1997 model Shaw and Rudy have built upon the 1995 Zeng et al version of the 1994 Luo-Rudy Dynamic Ventricular Model. In addition to the slow and fast components of the delayed rectifier K+ current, (IKr and IKs) and the T-type Calcium channel (ICa(T)), Shaw and Rudy have included an ATP-dependent potassium current (IK(ATP)) in their model. In turn, Viswanathan et al develop this model to include two activation gates (Xs1 and Xs2) into the formulation of IKs.
cell diagram of the shaw and viswanathan models showing ionic currents, pumps and exchangers within the sarcolemma and the sarcoplasmic reticulum
In this version of the 1994 Luo-Rudy Dynamic Ventricular Model, Faber and Rudy have built upon the 1999 Viswanathan model and they have added a sodium-dependent potassium current (IK(Na)).
cell diagram
In this most recent version of the 1994 Luo-Rudy Dynamic Ventricular Model, the model has been extended to include a transient outward potassium current (Ito) and also the eqautions for the Irel current have been updated.
state diagram
In this model, Livshitz and Rudy have merged the Luo-Rudy dynamic (LRd) and Hund-Rudy dynamic
(HRd) models of mammalian ventricular AP. This is a schematic diagram of the currents and the ion exchanges described by this merged model.
All the original paper references are cited below. Note that the CellML model described here is not based on a single publication per se. Rather, it is mainly based upon the 2000 Faber and Rudy model, with the addition of a transient outward potassium current (Ito) and also the eqautions for the Irel current have been updated. These modifications were based on the LRd07 Matlab code, which can be downloaded from the Rudy Research Lab website
Two Components of the Delayed Rectifier K+ Current in Ventricular Myocytes of the Guinea Pig Type, Jinglin Zeng, Kenneth R. Laurita, David S. Rosenbaum and Yoram Rudy, 1995,
Circulation Research
, 77, 140-152. (The full text version of the article is available for Journal Members on the Circulation Research website.) PubMed ID: 7788872
Electrophysiological effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration, Robin M. Shaw and Yoram Rudy, 1997,
Cardiovascular Research
, 35, 256-272. Full text and PDF versions of the article are available to subscribers on the Science Direct website. PubMed ID: 9349389
Effects of IKr and IKs Heterogeneity on Action Potential Duration and Its Rate Dependence: A Simulation Study, Prakash C. Viswanathan, BE; Robin M. Shaw, PhD; and Yoram Rudy, PhD, 1999,
Circulation
, 99, 2466-2474. (Full text and PDF versions of the article are available for Journal Members on the Circulation website.) PubMed ID: 10318671
Action Potential and Contractility in [Na+]i Overloaded Cardiac Myocytes, Gregory M. Faber and Yoram Rudy, 2000,
Biophysical Journal
, 78, 2392-2404. (Full text and PDF versions of the article are available for Journal Members on the Biophysical Journal website.) PubMed ID: 10777735
Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents, Leonid M. Livshitz and Yoram Rudy, 2007,
American Journal of Physiology: Heart and Circulatory Physiology
, 292, H2854-H2866. ( Full text and PDF versions of this article are available to subscribers on the American Journal of Physiology: Heart and Circulatory Physiology website). PubMed ID: 17277017
The University of Auckland
Auckland Bioengineering Institute
Catherine Lloyd
Auckland Bioengineering Institute, The University of Auckland
This model has been curated and is known to run in PCEnv and COR to recreate the published results. The units have been checked and are known to be consistent.
The CellML model has been based on a translation of the LRd07 Matlab code which can be downloaded from the Rudy lab website. It is basically the Faber and Rudy 2000 model with the addition of a transient potassium current (Ito) and an updated Irel current.
j.ashton@auckland.ac.nz
keyword
excitation-contraction coupling
Ventricular Myocyte
calcium
electrophysiology
cardiac
pathology
ventricular myocyte
Y
Rudy
Jesse
Ashton
Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study
78
2392
2404
2000-05-00 00:00
Biophysical Journal
2008-08-01T00:00:00+00:00
10777735
G
Faber
M