title: Stochastic binding of Ca2+ ions in the dyadic cleft; continuous versus random walk description of diffusion.
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.
authors.affiliation: Simula Research Laboratory, Lysaker, Norway. hake@simula.no
authors.forename: Johan
authors.initials: J
authors.lastname: Hake
authors.forename: Glenn T
authors.initials: GT
authors.lastname: Lines
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000737:chemistry*; D020013:Calcium Signaling; D004058:Diffusion; D007477:Ions; D021962:Membrane Microdomains / Q000737:chemistry* / Q000502:physiology; D008954:Models, Biological; D008956:Models, Chemical; D015233:Models, Statistical; D032383:Myocytes, Cardiac / Q000737:chemistry* / Q000502:physiology; D019897:Periplasm / Q000737:chemistry* / Q000502:physiology; D013269:Stochastic Processes
chemical_list: D007477:Ions; D002118:Calcium