Hinch, Greenstein, Tanskanen, Xu, Winslow, 2004
Model Status
This model is known to run in PCEnv and COR to reproduce the output shown in the publication. A PCEnv session file is also associated with this model.
Model Structure
This CellML model was based on the December 2004 paper:
"A Quantitative Analysis of Cardiac Myocyte Relaxation: A Simulation Study" by Hinch, Greenstein, Tanskanen, Xu and Winslow.
The following is the abstract of this paper:
Calcium (Ca2+)-induced Ca2+ release (CICR) in cardiac myocytes exhibits high gain and is graded. These properties result from local control of Ca2+ release. Existing local control models of Ca2+ release in which interactions between L-Type Ca2+ channels (LCCs) and ryanodine-sensitive Ca2+ release channels (RyRs) are simulated stochastically are able to reconstruct these properties, but only at high computational cost. Here we present a general analytical approach for deriving simplified models of local control of CICR, consisting of low-dimensional systems of coupled ordinary differential equations, from these more complex local control models in which LCC-RyR interactions are simulated stochastically. The resulting model, referred to as the coupled LCC-RyR gating model, successfully reproduces a range of experimental data, including L-Type Ca2+ current in response to voltage-clamp stimuli, inactivation of LCC current with and without Ca2+ release from the sarcoplasmic reticulum, voltage-dependence of excitation-contraction coupling gain, graded release, and the force-frequency relationship. The model does so with low computational cost.
The complete original publication reference is cited below:
A Simplified Local Control Model of Calcium-Induced Calcium Release in Cardiac Ventricular Myocytes, R. Hinch, J.R. Greenstein, A.J. Tanskanen, L. Xu, R.L. Winslow, 2004 Biophysical Journal , Volume 87 pp.3723-3736, PubMed ID: 15465866
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Schematic diagram of the currents and the ion exchanges described by the cardiac ventricular myocyte model. |
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The nine-state Markov model of the calcium release unit (CaRU). In state yij, the LCC is in the state i and the RyR is in the state j. |