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

Robert Hinch, J. L. Greenstein, A. J. Tanskanen, L. Xu, R. L. Winslow

Research output: Contribution to journalArticlepeer-review

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 Ca 2+ 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.

Original languageEnglish (US)
Pages (from-to)3723-3736
Number of pages14
JournalBiophysical journal
Volume87
Issue number6
DOIs
StatePublished - Dec 2004

ASJC Scopus subject areas

  • Biophysics

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