, Volume 41, Issue 6, pp 380–388 | Cite as

A Simulation Study of Calcium Dynamics Features Caused by Exchange between the Cytosol and Organellar Stores of Neurons

  • T. S. Novorodovskaya

The objects of the study were single-compartment mathematical models corresponding to a fragment of the dendrite of a cerebellar Purkinje neuron. The fragments contained the mitochondria (model 1) or a cistern of the endoplasmic reticulum, ER (model 2), functioning as calcium stores. With simulating single excitatory synaptic actions, we examined the dependence of the dynamics of intracellular Ca2+ levels on the maximum rate of Ca2+ exchange between the cytosol and these stores, as well as on the intensity of the diffusion flow into adjacent organelle-free regions. The plasma membrane of the compartment had ion channels (including those of the synaptic current) and the calcium pump characteristic of the mentioned neurons. The model equations took into account Ca2+ exchange between the cytosol, extracellular environment, and organellar stores, as well as the diffusion process. In model 1, the mitochondria exchanged Ca2+ with the cytosol through the uniporter and sodium-calcium exchanger; mitochondrial processes, such as the tricarboxylic acid cycle and aerobic cellular respiration, were also included. In model 2, the ER membrane had the calcium pump, leak channels, and channels of calcium-induced and inositol-3-phosphate-dependent Ca2+ release. The stores (mitochondria or ER) occupied 36% of the total volume of the compartment. An increase in the maximum rate of calcium exchange with the stores led to a proportional decrease in the peak Ca2+ concentrations in the cytosol ([Ca2+]i), more pronounced in the case of the ER; the Ca2+ concentration in both types of stores increased significantly. Due to the higher storage rate, the ER was able to absorb several times greater amounts of Ca2+ than the mitochondria did. With smaller diffusion flux (e.g., similarly to the case of diffusion from a larger-sized head into the neck of the dendritic spine), the intensity of cytosolic transients increased at fixed kinetics of flux exchange with the stores. Therefore, the organellar stores can significantly modulate not only the intensity but also the time course of changes in the intracellular Ca2+ levels.


dendrite dynamics of Ca2+ level calcium stores mitochondria endoplasmic reticulum transport molecules 


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  1. 1.
    P. G. Kostyuk and A. Verkhratsky, Calcium Signalling in the Nervous System, Wiley, Chichester (1995).Google Scholar
  2. 2.
    M. J. Brridge, “Neuronal calcium signalling,” Neuron, 21, No. 1, 13–26 (1998).CrossRefGoogle Scholar
  3. 3.
    Calcium as a Cellular Regulator, E. Carafli and C. Klee (eds.), Oxford Univ. Press, New York (1999).Google Scholar
  4. 4.
    L. D. Pizzo-Miller, J. A. Connor, and S. B. Andrews, “Microheterogeneity of calcium signalling in dendrites,” J. Physiol., 525, 53–61 (2000).CrossRefGoogle Scholar
  5. 5.
    C. A. Ross, J. Meldolesi, T. A. Milner, et al., “Inositol 1,4,5-trisphosphate receptor localized to endoplasmic reticulum in cerebellar Purkinje neurons,” Nature, 339, No. 6224, 468–470 (1989).CrossRefPubMedGoogle Scholar
  6. 6.
    K. Takei, G. A. Mignery, E. Mugnaini, et al., “Inositol 1,4,5-trisphosphate receptor causes formation of ER cisternal stacks in transfected fibroblasts and in cerebellar Purkinje cells,” Neuron, 12, 327–342 (1994).CrossRefPubMedGoogle Scholar
  7. 7.
    A. Verkhratsky, “Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons,” Physiol. Rev., 85, 201–279 (2005).CrossRefPubMedGoogle Scholar
  8. 8.
    M. Montero, M. Brini, R. Marsault, et al., “Monitoring dynamic changes in free Ca2+ concentration in the endoplasmic reticulum of intact cells,” J. EMBO, 14, 5467–5475 (1995).Google Scholar
  9. 9.
    M. J. Barrero, M. Montero, and J. Alvarez, “Dynamics of [Ca2+] in the endoplasmic reticulum and cytoplasm of intact HeLa cells: a comparative study,” J. Biol. Chem., 272, 27694–27699 (1997).CrossRefPubMedGoogle Scholar
  10. 10.
    S. Leo, K. Bianchi, M. Brini, and R. Rizzuto, “Mitochondrial calcium signalling in cell death,” J. FEBS, 272, No. 16, 4013–4022 (2005).CrossRefGoogle Scholar
  11. 11.
    R. Rizzuto, C. Bastianutto, M. Brini, et al., “Mitochondrial Ca2+ homeostasis in intact cells,” J. Cell. Biol., 126, 1183–1194 (1994).CrossRefPubMedGoogle Scholar
  12. 12.
    M. Montero, M. T. Alonso, E. Carnicero, et al., “Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate secretion,” Nat. Cell. Biol., 2, 57–61 (2000).CrossRefPubMedGoogle Scholar
  13. 13.
    R. Rizzuto and T. Pozzan, “Microdomains of intracellular Ca2+: molecular determinants and functional consequences,” Physiol. Rev., 86, No. 1, 369–408 (2006).CrossRefPubMedGoogle Scholar
  14. 14.
    N. B. Pivovarova, J. Hongpaisan, S. B. Andrews, et al., “Depolarization-induced mitochondrial Ca accumulation in sympathetic neurons: spatial and temporal characteristics,” J. Neurosci., 19, 6372–6384 (1999).PubMedGoogle Scholar
  15. 15.
    K. T. Baron, G. J. Wang, R. A. Padua, et al., “NMDA-evoked consumption and recovery of mitochondrially targeted aequorin suggests increased Ca2+ uptake by a subset of mitochondria in hippocampal neurons,” Brain Res., 993, 124–132 (2003).CrossRefPubMedGoogle Scholar
  16. 16.
    T. J. Collins, M. J. Berridge, P. Lipp, et al., “Mitochondria are morphologically and functionally heterogeneous within cells,” J. EMBO, 21, No. 7, 1616–1627 (2002).CrossRefGoogle Scholar
  17. 17.
    T. J. Collins and M. D. Bootman, “Mitochondria are morphologically heterogeneous within cells,” J. Exp. Biol., 206, No. 12, 1993–2000 (2003).CrossRefPubMedGoogle Scholar
  18. 18.
    T. J. Collins, P. Lipp, and M. J. Berridge, “Mitochondrial Ca2+ uptake depends on the spatial and temporal profile of cytosolic Ca2+ signals,” J. Biol. Chem., 276, 26411–26420 (2001).CrossRefPubMedGoogle Scholar
  19. 19.
    E. J. Kaftan, T. Xu, R. F. Abercrombie, et al., “Mitochondria shape hormonally induced cytoplasmic calcium oscillations and modulate exocytosis,” J. Biol. Chem., 275, 25465–25470 (2000).CrossRefPubMedGoogle Scholar
  20. 20.
    R. M. Drummond, T. Mix, R. A. Tuft, et al., “Mitochondrial Ca2+ homeostasis during Ca2+ influx and Ca2+ release in gastric myocytes from Bufo marinus,” J. Physiol., 522, 375–390 (2000).CrossRefPubMedGoogle Scholar
  21. 21.
    Q. A. Liu and H. Shio, “Mitochondrial morphogenesis, dendrite development and synapse formation in cerebellum require both Bcl-w and the glutamate receptor d2,” PLoS Genet., 4, No. 6, 1–13 (2008).CrossRefGoogle Scholar
  22. 22.
    V. Y. Polyakov, M. Y. Soukhomlinova, and D. Fais, “Fusion, fragmentation, and fission of mitochondria,” J. Biochem., 68, 838–849 (2003).Google Scholar
  23. 23.
    K. Okamoto and J. M. Shaw, “Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes,” Annu. Rev. Genet., 39, 503–536 (2005).CrossRefPubMedGoogle Scholar
  24. 24.
    D. C. Chan, “Mitochondrial fusion and fission in mammals,” Annu. Rev. Cell. Dev. Biol., 22, 79–99 (2006).CrossRefPubMedGoogle Scholar
  25. 25.
    B. Alberts, A. Johnson, J. Lewis, et al., “Molecular biology of the cell,” GS Garl. Sci. Taylor Francis Gr., 4, 808–821 (2002).Google Scholar
  26. 26.
    R. J. Youle and M. Karbowski, “Mitochondrial fission in apoptosis,” Nat. Rev. Mol. Cell Biol., 6, 657–663 (2005).CrossRefPubMedGoogle Scholar
  27. 27.
    E. Bossy-Wetzel, M. Barsoum, A. Godzik, et al., “Mitochondrial fission in apoptosis, neurodegeneration and aging,” Curr. Opin. Cell Biol., 15, 706–716 (2003).CrossRefPubMedGoogle Scholar
  28. 28.
    Z. Li, K. I. Okamoto, Y. Hayashi, et al., “The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses,” Cell, 119, 873–887 (2004).CrossRefPubMedGoogle Scholar
  29. 29.
    G. L. Rintoul, A. J. Filiano, J. B. Brocard, et al., “Glutamate decreases mitochondrial size and movement in primary forebrain neurons,” J. Neurosci., 23, 7881–7888 (2003).PubMedGoogle Scholar
  30. 30.
    P. Volpe, A. Nori, A. Martini, et al., “Multiple/heterogeneous Ca2+ stores in cerebellum Purkinje neurons,” Comp. Biochem. Physiol. Comp. Physiol., 105, No. 2, 205–211 (1993).CrossRefPubMedGoogle Scholar
  31. 31.
    S. M. Kogorod and T. S. Novorodovskaya, “Impact of geometrical characteristics of the organellar store and organelle-free cytosol on intracellular calcium dynamics in the dendrite: a simulation study,” Neurophysiology, 41, No. 1, 16–27 (2009).CrossRefGoogle Scholar
  32. 32.
    T. S. Novorodovskaya and S. M. Kogorod, “Comparative model analysis of calcium exchange between the cytosol and stores of mitochondria or endoplasmic reticulum,” Neurophysiology, 41, No. 5, 367–380 (2009).CrossRefGoogle Scholar
  33. 33.
    N. T. Carnevale and M. L. Hines, The NEURON Book, Cambridge Univ. Press, Cambridge (2006).Google Scholar
  34. 34.
    I. B. Kulagina, S. M. Korogod, G. Horcholle-Bossavit, et al., “The electro-dynamics of the dendritic space in Purkinje cells of the cerebellum,” Arch. Ital. Biol., 145, Nos. 3/4, 211–233 (2007).PubMedGoogle Scholar
  35. 35.
    S. Cortassa, M. A. Aon, E. Marban, et al., “An integrated model of cardiac mitochondrial energy metabolism and calcium dynamics,” J. Biophys., 84, 2734–2755 (2003).CrossRefGoogle Scholar
  36. 36.
    E. De Schutter and P. Smolen, “Calcium dynamics in large neuronal models,” in: Methods in Neuronal Modeling: from Ions to Networks, C. Koch and I. Segev (eds.), MIT Press, Cambridge (1998), pp. 211–250.Google Scholar
  37. 37.
    G. Magnus and J. Keizer, “Minimal model of b-cell Ca2+ handling,” Am. J. Physiol., 273, 717–733 (1997).Google Scholar
  38. 38.
    G. Magnus and J. Keizer, “Model of b-cell mitochondrial calcium handling and electrical activity. I. Cytoplasmic variables,” Am. J. Physiol., 274, 1158–1173 (1998).Google Scholar
  39. 39.
    G. Magnus and J. Keizer, “Model of b-cell mitochondrial calcium handling and electrical activity. II. Mitochondrial variables,” Am. J. Physiol., 274, 1174–1184 (1998).Google Scholar
  40. 40.
    E. Neher, “Details of Ca2+ dynamics matter,” J. Physiol., 586, No. 8, 2031 (2008).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2009

Authors and Affiliations

  1. 1.Oles’ Gonchar Dnepropetrovsk National UniversityDnepropetrovskUkraine

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