Shannon, Wang, Puglisi, Weber, Bers, 2004

Model Status

This model runs in PCEnv, OpenCell and COR to recreate the published results. The units are consistent throughout. The model equations and output were checked using the original matlab code, and it currently recreates the Pace1 Stimulus protocol described.

Model Structure

ABSTRACT: We have developed a detailed mathematical model for Ca2+ handling and ionic currents in the rabbit ventricular myocyte. The objective was to develop a model that: 1), accurately reflects Ca-dependent Ca release; 2), uses realistic parameters, particularly those that concern Ca transport from the cytosol; 3), comes to steady state; 4), simulates basic excitation-contraction coupling phenomena; and 5), runs on a normal desktop computer. The model includes the following novel features: 1), the addition of a subsarcolemmal compartment to the other two commonly formulated cytosolic compartments (junctional and bulk) because ion channels in the membrane sense ion concentrations that differ from bulk; 2), the use of realistic cytosolic Ca buffering parameters; 3), a reversible sarcoplasmic reticulum (SR) Ca pump; 4), a scheme for Na-Ca exchange transport that is [Na]i dependent and allosterically regulated by [Ca]i; and 5), a practical model of SR Ca release including both inactivation/adaptation and SR Ca load dependence. The data describe normal electrical activity and Ca handling characteristics of the cardiac myocyte and the SR Ca load dependence of these processes. The model includes a realistic balance of Ca removal mechanisms (e.g., SR Ca pump versus Na-Ca exchange), and the phenomena of rest decay and frequency-dependent inotropy. A particular emphasis is placed upon reproducing the nonlinear dependence of gain and fractional SR Ca release upon SR Ca load. We conclude that this model is more robust than many previously existing models and reproduces many experimental results using parameters based largely on experimental measurements in myocytes.

The complete original paper reference is cited below:

A mathematical treatment of integrated Ca dynamics within the ventricular myocyte, Thomas R. Shannon, Fei Wang, Jose Puglisi, Christopher Weber and Donald M. Bers, 2004, Biophysical Journal, 87, 3351-3371. PubMed ID: 15347581

A schematic diagram of the cell model which highlights the calcium- and sodium-dependent components of the model in particular.