A Simplified Local Control Model of Calcium-Induced Calcium Release in Cardiac Ventricular Myocytes

Model Status

This model is known to run in OpenCell and COR to reproduce the output shown in the publication.

Model Structure

ABSTRACT: 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 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, 87, 3723-3736, PubMed ID: 15465866

Schematic diagram of the currents and the ion exchanges described by the cardiac ventricular myocyte model.

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.