Effects of IKr and IKs Heterogeneity on Action Potential Duration and Its Rate Dependence

Effects of IKr and IKs Heterogeneity on Action Potential Duration and Its Rate Dependence

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

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 below. 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 Case Western Reserve University (To view this website, follow this link: http://www.cwru.edu/med/CBRTC/LRdOnline/development.htm

A schematic diagram describing the current flows across the cell membrane that are captured in the original, 1994 Luo-Rudy II, dynamic model.
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.
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.

All the original paper references are cited below:

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

In this most recent 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)).
The network defined in the CellML description of the most recent version of the Luo-Rudy II model. A key describing the significance of the shapes of the components and the colours of the connections between them is in the notation guide. For simplicity, not all the variables are shown.