AuthorsJ. E. Hake and G. T. Lines
TitleStochastic Binding of Ca2+ in the Dyadic Cleft: Continuous Vs. Random-Walk Description of Diffusion.
AfilliationCenter for Biomedical Computing (SFF), Cardiac Modeling, Scientific Computing
Project(s)Center for Biomedical Computing (SFF)
StatusPublished
Publication TypeJournal Article
Year of Publication2008
JournalBiophysical Journal
Volume94
Number11
Pagination4184-4201
Date Publishedjuni
Abstract

Ca2+ signaling in the dyadic cleft in ventricular myocytes is fundamentally discrete and stochastic. We study the stochastic binding of single Ca2+ 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 Ca2+ signaling in the dyadic cleft, determined by single binding events, can be described using a deterministic model of Ca2+ 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.

DOI10.1529/biophysj.106.103523
Citation KeySimula.SC.40