title: Modulation of elementary calcium release mediates a transition from puffs to waves in an IP3R cluster model.
abstract: The oscillating concentration of intracellular calcium is one of the most important examples for collective dynamics in cell biology. Localized releases of calcium through clusters of inositol 1,4,5-trisphosphate receptor channels constitute elementary signals called calcium puffs. Coupling by diffusing calcium leads to global releases and waves, but the exact mechanism of inter-cluster coupling and triggering of waves is unknown. To elucidate the relation of puffs and waves, we here model a cluster of IP3R channels using a gating scheme with variable non-equilibrium IP3 binding. Hybrid stochastic and deterministic simulations show that puffs are not stereotyped events of constant duration but are sensitive to stimulation strength and residual calcium. For increasing IP3 concentration, the release events become modulated at a timescale of minutes, with repetitive wave-like releases interspersed with several puffs. This modulation is consistent with experimental observations we present, including refractoriness and increase of puff frequency during the inter-wave interval. Our results suggest that waves are established by a random but time-modulated appearance of sustained release events, which have a high potential to trigger and synchronize activity throughout the cell.
authors.affiliation: Institut für Physik, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Rückl
authors.affiliation: Departments of Neurobiology and Behavior, Physiology and Biophysics, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Ian
authors.initials: I
authors.lastname: Parker
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Marchant
authors.affiliation: Johann Radon Institute for Computational and Applied Mathematics, Austrian Academy of Sciences, Linz, Austria.
authors.forename: Chamakuri
authors.initials: C
authors.lastname: Nagaiah
authors.affiliation: Neuroscience Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Johenning
authors.affiliation: Institut für Physik, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Sten
authors.initials: S
authors.lastname: Rüdiger
mesh_terms: D002118:Calcium / Q000737:chemistry* / Q000378:metabolism*; D019295:Computational Biology; D003198:Computer Simulation; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D002118:Calcium