Shiferaw, Watanabe, Garfinkel, Weiss, Karma, 2003

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 the figure 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 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

A schematic diagram of the intracellular compartments relevant to calcium cycling in ventricular myocytes.