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A Quantitative Model of ATP-Mediated Calcium Wave Propagation in Astrocyte Networks

  • William G. Gibson
  • Les Farnell
  • Max R. Bennett
Part of the Modeling and Simulation in Science, Engineering and Technology book series (MSSET)

Summary

In the past attention has mainly been focused on neurons and the role they play, both individually and as parts of networks, in the functioning of the brain and nervous system. However, glial cells outnumber neurons in the brain, and it is now becoming apparent that, far from just performing supportive and housekeeping tasks, they are also actively engaged in information processing and possibly even learning. Communication in glial cells is manifested by waves of calcium ions (Ca2+) that are released from internal stores, and these waves are observed experimentally using fluorescent markers attached to the ions. The waves can be initiated by stimulation of a single cell, and initially it was assumed that the transmission mechanism involved the passage of an intercellular signalling agent passing through gap junctions connecting the cells. However, a surprising feature is that in many cases the calcium waves can cross cell-free zones, thus indicating the presence of an extracellular messenger.

We have constructed a mathematical model of calcium wave propagation in networks of model astrocytes, these being a subclass of glial cells. The extracellular signalling agent is ATP (adenosine triphosphate) and it acts on metabotropic purinergic receptors on the astrocytes, initiating a G-protein cascade leading to the production of inositol trisphosphate (IP3) and the subsequent release of Ca2+ from intracellular stores via IP3-sensitive channels. Stimulation of one cell (by a pulse of ATP or by raising the IP3 level) leads to the regenerative release of ATP both from this cell and from neighbouring cells, and hence a Ca2+ wave. Results are given for the propagation of Ca2+ waves in two-dimensional arrays of model astrocytes and also in lanes with cell-free zones in between. These theoretical considerations support the concept of extracellular purinergic transmission in astrocyte networks.

Keywords

Astrocyte calcium inositol trisphosphate ATP G-protein cascade extracellular signalling 

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References

  1. 1.
    Abdipranoto, A., Liu, G.J., Werry, E.L., Bennett, M.R.: Mechanisms of secretion of ATP from cortical astrocytes triggered by uridine triphosphate. Neuroreport, 14, 2177–81 (2003).CrossRefGoogle Scholar
  2. 2.
    Anderson, C.M., Bergher, J.P., Swanson, R.A.: ATP-induced ATP release from astrocytes. J. Neurochem., 88, 246–56 (2004).CrossRefGoogle Scholar
  3. 3.
    Araque, A., Parpura, V., Sanzgiri, R.P., Haydon, P.G.: Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci., 22, 208–215 (1999).CrossRefGoogle Scholar
  4. 4.
    Charles, A.C., Merrill, J.E., Dirksen, E.R., Sanderson, M.J.: Intercellular signaling in glial cells: Calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron., 6, 983–992 (1991).CrossRefGoogle Scholar
  5. 5.
    Coco, S., Calegari, F., Pravettoni, E., Pozzi, D., Taverna, E., Rosa, P.,Matteoli, M., Verderio, C.: Storage and release of ATP from astrocytes in culture. J. Biol. Chem., 278, 1354–62 (2003).CrossRefGoogle Scholar
  6. 6.
    Cornell-Bell, A.H., Finkbeiner, S.M., Cooper, M.S., Smith, S.J.: Glutamate induces calcium waves in cultured astrocytes: long-range glial signalling. Science, 247, 470–473 (1990).CrossRefGoogle Scholar
  7. 7.
    Cotrina, M.L, Lin, J.H., Alves-Rodrigues, A., Liu, S., Li, J., Azmi-Ghadimi, H., Kang, J., Naus, C.C., Nedergaard, M.: Connexins regulate calcium signaling by controlling ATP release. Proc. Natl. Acad. Sci. U.S.A., 95, 15735–40 (1998).CrossRefGoogle Scholar
  8. 8.
    De Young, G.W., Keizer J.: A single-pool inositol 1,4,5-trisphosphate-receptor-based model for agonist-stimulated oscillations in Ca2+ concentration. Proc. Natl. Acad. Sci. U.S.A., 89, 9895–9 (1992).CrossRefGoogle Scholar
  9. 9.
    Fellin, T., Carmignoto, G.: Neurone to astrocyte signalling in the brain represents a distinct multifunctional unit. J. Physiol., 559, 3–15 (2004).CrossRefGoogle Scholar
  10. 10.
    Fink, C.F., Slepchenko, B., Loew, L.M.: Determination of time-dependent inositol-1,4,5- trisphosphate concentrations during calcium release in a smooth muscle cell. Biophys. J., 77, 617–628 (1999).CrossRefGoogle Scholar
  11. 11.
    Gallagher, C.J., Salter, M.W.: Differential properties of astrocyte calcium waves mediated by P2Y1 and P2Y2 receptors. J. Neurosci., 23, 6728–39 (2003).Google Scholar
  12. 12.
    Hassinger, T.D., Guthrie, P.B., Atkinson, P.B., Bennett, M.V., Kater, S.B.: An extracellular signaling component in propagation of astrocytic calcium waves. Proc. Natl. Acad. Sci. U.S.A., 93, 13268–73 (1996).CrossRefGoogle Scholar
  13. 13.
    Henery, R., Gibson, W.G., Bennett, M.R.: Quantal currents and potential in the threedimensional anisotropic bidomain model of smooth muscle. Bull. Math. Biol., 59, 1047–1075 (1997).zbMATHCrossRefGoogle Scholar
  14. 14.
    Höfer, T., Venance, L., Giaume, C.: Control and plasticity of intercellular calcium waves in astrocytes: a modeling approach. J. Neurosci., 22, 4850–9 (2002).Google Scholar
  15. 15.
    Lemon, G., Gibson,W.G., Bennett, M.R.: Metabotropic receptor activation, desensitization and sequestration-I: modelling calcium and inositol 1,4,5-trisphosphate dynamics following receptor activation. J. Theor. Biol., 223, 93–111 (2003).CrossRefMathSciNetGoogle Scholar
  16. 16.
    Li, Y-X., Rinzel, J.: Equations for InsP3 receptor-mediated [Ca2+] oscillations derived from a detailed kinetic model: a Hodgkin-Huxley like formalism. J. Theor. Biol., 166, 461–473 (1994).CrossRefGoogle Scholar
  17. 17.
    Newman, E.A.: Propagation of intercellular calcium waves in retinal astrocytes and Müller cells. J. Neurosci., 21, 2215–2223 (2001).Google Scholar
  18. 18.
    Niggel, J., Sigurdson, W., Sachs, F.: Mechanically induced calcium movements in astrocytes, bovine aortic endothelial cells and C6 glioma cells. Membrane Biology, 174, 121–134 (2000).CrossRefGoogle Scholar
  19. 19.
    Porter, J.T., McMarthy, K.D.: Astrocyte neurotransmittter receptors in situ and in vivo. Prog. Neurobiol., 51, 439–455 (1997).CrossRefGoogle Scholar
  20. 20.
    Sneyd, J., Wilkins, M., Strahonja, A., Sanderson, M.J. : Calcium waves and oscillations driven by an intercellular gradient of inositol (1,4,5)-trisphosphate. Biophys. Chem., 72, 101–109 (1998).CrossRefGoogle Scholar
  21. 21.
    Wang, Z., Haydon, P.G., and Yeung, E.S.: Direct observation of calcium-independent intercellular ATP signaling in astrocytes. Anal. Chem., 72, 2001–7 (2000).CrossRefGoogle Scholar

Copyright information

© Birkhäuser Boston 2008

Authors and Affiliations

  • William G. Gibson
    • 1
  • Les Farnell
    • 1
  • Max R. Bennett
    • 2
  1. 1.School of Mathematics and Statistics, The University of Sydney, N.S.W. 2006Australia
  2. 2.Department of PhysiologyThe University of Sydney, N.S.W. 2006Australia

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