Stochastic binding of Ca2+ ions in the dyadic cleft; continuous versus random walk description of diffusion

Biophys J. 2008 Jun;94(11):4184-201. doi: 10.1529/biophysj.106.103523. Epub 2008 Feb 8.

Abstract

Ca(2+) signaling in the dyadic cleft in ventricular myocytes is fundamentally discrete and stochastic. We study the stochastic binding of single Ca(2+) ions to receptors in the cleft using two different models of diffusion: a stochastic and discrete Random Walk (RW) model, and a deterministic continuous model. We investigate whether the latter model, together with a stochastic receptor model, can reproduce binding events registered in fully stochastic RW simulations. By evaluating the continuous model goodness-of-fit for a large range of parameters, we present evidence that it can. Further, we show that the large fluctuations in binding rate observed at the level of single time-steps are integrated and smoothed at the larger timescale of binding events, which explains the continuous model goodness-of-fit. With these results we demonstrate that the stochasticity and discreteness of the Ca(2+) signaling in the dyadic cleft, determined by single binding events, can be described using a deterministic model of Ca(2+) diffusion together with a stochastic model of the binding events, for a specific range of physiological relevant parameters. Time-consuming RW simulations can thus be avoided. We also present a new analytical model of bimolecular binding probabilities, which we use in the RW simulations and the statistical analysis.

Publication types

  • Evaluation Study

MeSH terms

  • Binding Sites
  • Calcium / chemistry*
  • Calcium Signaling*
  • Diffusion
  • Ions
  • Membrane Microdomains / chemistry*
  • Membrane Microdomains / physiology
  • Models, Biological*
  • Models, Chemical*
  • Models, Statistical
  • Myocytes, Cardiac / chemistry*
  • Myocytes, Cardiac / physiology
  • Periplasm / chemistry*
  • Periplasm / physiology
  • Stochastic Processes

Substances

  • Ions
  • Calcium