Modelling Intracellular Calcium Cycling in Ventricular Myocytes
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
Model Structure
Cardiac myocyte contraction is stimulated by a rise in the concentration of intracellular calcium ([Ca2+]i), which in turn is due to the coordinated release of calcium from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyR). These receptors are close to the L-type calcium channels in the cell surface membrane, and when the cell is depolarised, the calcium that enters the cell through the L-type channels is confined within a microdomain (the dyadic junction). The RyR then sense this increase in [Ca2+]i and respond by opening and releasing more calcium from the SR in a process known as calcium-induced calcium releases (CICR). The cell's contractile elements are activated by this increase in [Ca2+]i and the cell contracts. A calcium-activated uptake pump then pumps calcium back into the SR. This interaction between membrane potential and intracellular calcium cycling forms the basis of excitation-contraction (EC) coupling. The calcium system is driven by an action potential waveform that is itself dependent on the dynamics of the calcium system.
There have been several efforts to mathematically model intracellular calcium dynamics, such as:
Modelling the Functional Ca2+ Release Unit, 1999, Rice et al., 1999
Model of Ryanodine Receptor Gating in Cardiac Muscle, 1999, Stern et al.
Sobie et al. Mechanism of Cardiac Ca2+ Spark Termination, 2002
which focus on the detailed calcium dynamics within the dyadic junction. Several authors have developed models of calcium cycling at the whole cell level, including:
Luo-Rudy Ventricular Model II (dynamic), 1994
Jafri-Rice-Winslow Ventricular Model, 1998
Snyder et al., Cardiocyte Ca2+ Dynamics, 2000
However, some of these models are lacking in physiological detail; for example, some ignore intracellular calcium compartmentation, or they overlook the fact that calcium release from the SR is in fact the summation of several discrete events.
In the publication described here, Shiferaw et al. present a new model of EC coupling in ventricular myocytes (see below). In contrast to the previously published models this one represents calcium release from the SR as a summation of elementary release events that correspond to calcium sparks. In addition, the model includes features that are absent in the earlier models, such as:
a description of intracellular sodium accumulation;
compartmentation of myoplasm into a submembrane space near the sarcolemma, and the rest of the myoplasm; and
a calcium diffusional delay between the network SR (NSR) and the junctional SR (JSR)
The model has been described here in CellML (the raw CellML description of the Shiferaw et al. 2003 model can be downloaded in various formats as described in ).
The complete original paper reference is cited below:
Model of Intracellular Calcium Cycling in Ventricular Myocytes, Y. Shiferaw, M. A. Wantanabe, A. Garfinkel, J. N. Weiss, and A. Karma, 2003, Biophysical Journal, 85, 3666-3686. PubMed ID: 14645059
cell diagram
A schematic diagram of the intracellular compartments relevant to calcium cycling in ventricular myocytes.
calcium dynamics
cardiac
electrophysiology
ventricular myocyte
Ventricular Myocyte
Model of Intracellular Calcium Cycling in Ventricular Myocytes
85
3666
3686
2004-01-08
c.lloyd@auckland.ac.nz
This is the CellML description of Shiferaw et al.'s 2003 mathematical
model of intracellular calcium cycling in ventricular myocytes.
Shiferaw et al.'s 2003 mathematical model of intracellular calcium
cycling in ventricular myocytes.
Ventricular Myocyte
14645059
Catherine
Lloyd
May
Catherine Lloyd
Y
Shiferaw
2003-12
Biophysical Journal
A
Garfinkel
The University of Auckland
The Bioengineering Institute
keyword
A
Karma
J
Weiss
N
M
Watanabe
A
The University of Auckland, Bioengineering Institute