A simplified local control model of calcium induced calcium release in cadiac ventricular myocytes

¹ Oxford University
² Johns Hopkins University

^* To whom correspondence should be addressed. E-mail: hinch{at}maths.ox.ac.uk.

Submitted on July 16, 2004
Revised on August 16, 2004
Accepted on 21 September 2004

	Abstract

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

Key Words: calcium induced calcium release, cardiac modelling, cardiac myocytes, excitation-contraction coupling, graded release, local control models

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