A simplified local control model of calcium-induced calcium release in cardiac ventricular myocytes.

R. Hinch, J. Greenstein, A. Tanskanen, L. Xu, and R. Winslow. Biophys. J. 87 (6): 3723--3736 (December 2004)


Calcium (Ca$^2+$)-induced Ca$^2+$ release (CICR) in cardiac myocytes exhibits high gain and is graded. These properties result from local control of Ca$^2+$ release. Existing local control models of Ca$^2+$ release in which interactions between L-Type Ca$^2+$ channels (LCCs) and ryanodine-sensitive Ca$^2+$ 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 Ca$^2+$ current in response to voltage-clamp stimuli, inactivation of LCC current with and without Ca$^2+$ 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.


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