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

Biophys J. 2004 Dec;87(6):3723-36. doi: 10.1529/biophysj.104.049973. Epub 2004 Oct 1.

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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels, L-Type / physiology*
  • Calcium Signaling / physiology*
  • Cell Membrane / physiology*
  • Computer Simulation
  • Humans
  • Ion Channel Gating / physiology
  • Membrane Potentials / physiology
  • Models, Cardiovascular*
  • Myocardial Contraction / physiology
  • Myocytes, Cardiac / physiology*
  • Ryanodine Receptor Calcium Release Channel / physiology*
  • Ventricular Function

Substances

  • Calcium Channels, L-Type
  • Ryanodine Receptor Calcium Release Channel
  • Calcium