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In nonexcitable cells, global Ca2+ spikes emerge from the collective dynamics of clusters of Ca2+ channels that are coupled by diffusion. Current modeling approaches have opposed stochastic descriptions of these systems to purely deterministic models, while both paradoxically appear compatible with experimental data. Combining fully stochastic simulations and mean-field analyses, we demonstrate that these two approaches can be reconciled. Our fully stochastic model generates spike sequences that can be seen as noise-perturbed oscillations of deterministic origin, while displaying statistical properties in agreement with experimental data. These underlying deterministic oscillations arise from a phenomenological spike nucleation mechanism. © 2019 American Physical Society.


Documento: Artículo
Título:Deterministic Limit of Intracellular Calcium Spikes
Autor:Voorsluijs, V.; Dawson, S.P.; De Decker, Y.; Dupont, G.
Filiación:Nonlinear Physical Chemistry Unit, Center for Nonlinear Phenomena and Complex Systems (CENOLI), Université Libre de Bruxelles, Boulevard du Triomphe, C.P. 231, Brussels, B-1050, Belgium
Departamento de Física, FCEN-UBA and IFIBA, UBA-CONICET, Ciudad Universitaria, Pabellón i, Buenos Aires, 1428, Argentina
Unité de Chronobiologie Théorique, Université Libre de Bruxelles, Boulevard du Triomphe, C.P. 231, Brussels, B-1050, Belgium
Título revista:Physical Review Letters
Título revista abreviado:Phys Rev Lett


  • Berridge, M.J., Lipp, P., Bootman, M.D., The versatility and universality of calcium signalling (2000) Nat. Rev. Mol. Cell Biol., 1, p. 11
  • Dupont, G., Falcke, M., Kirk, V., Sneyd, J., (2016) Models of Calcium Signalling, 43. , Interdisciplinary Applied Mathematics (Springer International Publishing Switzerland
  • Shuai, J., Rose, H.J., Parker, I., The number and spatial distribution of (Equation presented) receptors underlying calcium puffs in Xenopus oocytes (2006) Biophys. J., 91, p. 4033
  • Wiltgen, S.M., Smith, I.F., Parker, I., Superresolution localization of single functional (Equation presented) channels utilizing (Equation presented) flux as a readout (2010) Biophys. J., 99, p. 437
  • Marchant, J.S., Parker, I., Role of elementary (Equation presented) puffs in generating repetitive (Equation presented) oscillations (2001) EMBO J., 20, p. 65
  • Lock, J.T., Smith, I.F., Parker, I., Comparison of (Equation presented) puffs evoked by extracellular agonists and photoreleased (Equation presented) (2017) Cell Calcium, 63, p. 43
  • Skupin, A., Kettenmann, H., Winkler, U., Wartenberg, M., Sauer, H., Tovey, S.C., Taylor, C.W., Falcke, M., How does intracellular (Equation presented) oscillate: By chance or by the clock? (2008) Biophys. J., 94, p. 2404
  • Thurley, K., Smith, I.F., Tovey, S.C., Taylor, C.W., Parker, I., Falcke, M., Timescales of (Equation presented)-evoked (Equation presented) spikes emerge from (Equation presented) puffs only at the cellular level (2011) Biophys. J., 101, p. 2638
  • Fraiman, D., Pando, B., Dargan, S., Parker, I., Dawson, S.P., Analysis of puff dynamics in oocytes: Interdependence of puff amplitude and interpuff interval (2006) Biophys. J., 90, p. 3897
  • Thul, R., Falcke, M., Stability of Membrane Bound Reactions (2004) Phys. Rev. Lett., 93, p. 188103
  • Thurley, K., Tovey, S.C., Moenke, G., Prince, V.L., Meena, A., Thomas, A.P., Skupin, A., Falcke, M., Reliable encoding of stimulus intensities within random sequences of intracellular (Equation presented) spikes (2014) Sci. Signal. (Online), 7, p. ra59
  • Politi, A., Gaspers, L.D., Thomas, A.P., Höfer, T., Models of (Equation presented) and (Equation presented) oscillations: Frequency encoding and identification of underlying feedbacks (2006) Biophys. J., 90, p. 3120
  • Falcke, M., Moein, M., Tilunaite, A., Thul, R., Skupin, A., On the phase space structure of (Equation presented) induced (Equation presented) signalling and concepts for predictive modeling (2018) Chaos, 28, p. 45115
  • Sneyd, J., Han, J.M., Wang, L., Chen, J., Yang, X., Tanimura, A., Sanderson, M.J., Yule, D.I., On the dynamical structure of calcium oscillations (2017) Proc. Natl. Acad. Sci. U.S.A., 114, p. 1456
  • Skupin, A., Falcke, M., From puffs to global (Equation presented) signals: How molecular properties shape global signals (2009) Chaos, 19, p. 37111
  • Tilunaite, A., Croft, W., Russell, N., Bellamy, T.C., Thul, R., A Bayesian approach to modelling heterogeneous calcium responses in cell populations (2017) PLoS Comput. Biol., 13, p. e1005794
  • Bugrim, A.E., Zhabotinsky, A.M., Epstein, I.R., Calcium waves in a model with a random spatially discrete distribution of (Equation presented) release sites (1997) Biophys. J., 73, p. 2897
  • Jung, P., Swaminathan, D., Ullah, A., Calcium spikes: Chance or necessity? (2010) Chem. Phys., 375, p. 625
  • Swillens, S., Dupont, G., Combettes, L., Champeil, P., From calcium blips to calcium puffs: Theoretical analysis of the requirements for interchannel communication (1999) Proc. Natl. Acad. Sci. U.S.A., 96, p. 13750
  • Bruno, L., Solovey, G., Ventura, A.C., Dargan, S., Dawson, S.P., Quantifying calcium fluxes underlying calcium puffs in Xenopus laevis oocytes (2010) Cell Calcium, 47, p. 273
  • Skupin, A., Kettenmann, H., Falcke, M., Calcium signals driven by single channel noise (2010) PLoS Comput. Biol., 6, p. e1000870
  • Calabrese, A., Fraiman, D., Zysman, D., Ponce Dawson, S., Stochastic fire-diffuse-fire model with realistic cluster dynamics (2010) Phys. Rev. e, 82, p. 31910
  • Bootman, M.D., Berridge, M.J., Lipp, P., Cooking with calcium: The recipes for composing global signals from elementary events (1997) Cell, 91, p. 367
  • Lopez, L.F., Ponce Dawson, S., Luminal (Equation presented) dynamics during (Equation presented) mediated signals (2016) Phys. Biol., 13, p. 36006
  • Gillespie, D.T., Stochastic simulation of chemical kinetics (2007) Annu. Rev. Phys. Chem., 58, p. 35
  •, See Supplemental Material at for more information on the stochastic algorithm, derivation of the deterministic evolution equations, evolution of the coefficient of variation with respect to (Equation presented) and statistics of (Equation presented) relation for varying (Equation presented); Thomas, D., Lipp, P., Berridge, M.J., Bootman, M.D., Hormone-evoked elementary (Equation presented) signals are not stereotypic, but reflect activation of different size channel clusters and variable recruitment of channels within a cluster (1998) J. Biol. Chem., 273, p. 27130
  • Dupont, G., Abou-Lovergne, A., Combettes, L., Stochastic Aspects of Oscillatory (Equation presented) Dynamics in Hepatocytes (2008) Biophys. J., 95, p. 2193
  • Givré, A., Ponce Dawson, S., Information content in stochastic pulse sequences of intracellular messengers (2018) Front. Phys., 6, p. 74


---------- APA ----------
Voorsluijs, V., Dawson, S.P., De Decker, Y. & Dupont, G. (2019) . Deterministic Limit of Intracellular Calcium Spikes. Physical Review Letters, 122(8).
---------- CHICAGO ----------
Voorsluijs, V., Dawson, S.P., De Decker, Y., Dupont, G. "Deterministic Limit of Intracellular Calcium Spikes" . Physical Review Letters 122, no. 8 (2019).
---------- MLA ----------
Voorsluijs, V., Dawson, S.P., De Decker, Y., Dupont, G. "Deterministic Limit of Intracellular Calcium Spikes" . Physical Review Letters, vol. 122, no. 8, 2019.
---------- VANCOUVER ----------
Voorsluijs, V., Dawson, S.P., De Decker, Y., Dupont, G. Deterministic Limit of Intracellular Calcium Spikes. Phys Rev Lett. 2019;122(8).