A quantitative model of purinergic junctional transmission of calcium waves in astrocyte networks.

A principal means of transmitting intracellular calcium (Ca2+) waves at junctions between astrocytes involves the release of the chemical transmitter adenosine triphosphate (ATP). A model of this process is presented in which activation of purinergic P2Y receptors by ATP triggers the release of ATP, in an autocrine manner, as well as concomitantly increasing intracellular Ca2+. The dependence of the temporal characteristics of the Ca2+ wave are shown to critically depend on the dissociation constant (K(R)) for ATP binding to the P2Y receptor type. Incorporating this model astrocyte into networks of these cells successfully accounts for many of the properties of propagating Ca2+ waves, such as the dependence of velocity on the type of P2Y receptor and the time-lag of the Ca2+ wave behind the ATP wave. In addition, the conditions under which Ca2+ waves may jump from one set of astrocytes across an astrocyte-free lane to another set of astrocytes are quantitatively accounted for by the model. The properties of purinergic transmission at astrocyte junctions may determine many of the characteristics of Ca2+ propagation in networks of these cells.

[1]  M. Sanderson,et al.  Calcium waves and oscillations driven by an intercellular gradient of inositol (1,4,5)-trisphosphate. , 1998, Biophysical chemistry.

[2]  J. Rinzel,et al.  Equations for InsP3 receptor-mediated [Ca2+]i oscillations derived from a detailed kinetic model: a Hodgkin-Huxley like formalism. , 1994, Journal of theoretical biology.

[3]  C. Naus,et al.  Connexins regulate calcium signaling by controlling ATP release. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Salter,et al.  P2Y and P2U receptors differentially release intracellular Ca2+ via the phospholipase C/inositol 1,4,5-triphosphate pathway in astrocytes from the dorsal spinal cord , 1998, Neuroscience.

[5]  V. Gundersen,et al.  Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate , 2004, Nature Neuroscience.

[6]  S. P. Srinivas,et al.  ATP release through connexin hemichannels in corneal endothelial cells. , 2005, Investigative ophthalmology & visual science.

[7]  R. Lerner,et al.  The Sleep-inducing Lipid Oleamide Deconvolutes Gap Junction Communication and Calcium Wave Transmission in Glial Cells , 1997, The Journal of cell biology.

[8]  D. Spray,et al.  Acute downregulation of Cx43 alters P2Y receptor expression levels in mouse spinal cord astrocytes , 2003, Glia.

[9]  Jai-Yoon Sul,et al.  Astrocytic connectivity in the hippocampus. , 2004, Neuron glia biology.

[10]  G. Lemon,et al.  Metabotropic receptor activation, desensitization and sequestration-I: modelling calcium and inositol 1,4,5-trisphosphate dynamics following receptor activation. , 2003, Journal of theoretical biology.

[11]  J. Keizer,et al.  Ryanodine receptor adaptation and Ca2+(-)induced Ca2+ release-dependent Ca2+ oscillations. , 1996, Biophysical journal.

[12]  G. J. Liu,et al.  Mechanisms of secretion of ATP from cortical astrocytes triggered by uridine triphosphate , 2003, Neuroreport.

[13]  Laurent Venance,et al.  Mechanism Involved in Initiation and Propagation of Receptor-Induced Intercellular Calcium Signaling in Cultured Rat Astrocytes , 1997, The Journal of Neuroscience.

[14]  H Zimmermann,et al.  New insights into molecular structure and function of ecto-nucleotidases in the nervous system , 1998, Neurochemistry International.

[15]  S. Murphy,et al.  Purinergic P2Y receptors on astrocytes are directly coupled to phospholipase A2 , 1993, Glia.

[16]  J. Keizer,et al.  A single-pool inositol 1,4,5-trisphosphate-receptor-based model for agonist-stimulated oscillations in Ca2+ concentration. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Matteoli,et al.  Storage and Release of ATP from Astrocytes in Culture* , 2003, The Journal of Biological Chemistry.

[18]  E. Dere,et al.  Mice with astrocyte‐directed inactivation of connexin43 exhibit increased exploratory behaviour, impaired motor capacities, and changes in brain acetylcholine levels , 2003, The European journal of neuroscience.

[19]  L M Loew,et al.  Determination of time-dependent inositol-1,4,5-trisphosphate concentrations during calcium release in a smooth muscle cell. , 1999, Biophysical journal.

[20]  M. Salter,et al.  Differential Properties of Astrocyte Calcium Waves Mediated by P2Y1 and P2Y2 Receptors , 2003, The Journal of Neuroscience.

[21]  G. Burnstock,et al.  Characterization of the Ca2+ responses evoked by ATP and other nucleotides in mammalian brain astrocytes , 1997, British journal of pharmacology.

[22]  M. Zonta,et al.  Cytosolic Calcium Oscillations in Astrocytes May Regulate Exocytotic Release of Glutamate , 2001, The Journal of Neuroscience.

[23]  Q. Zhu,et al.  P2 purinoceptors in rat cortical astrocytes: Expression, calcium-imaging and signalling studies , 1996, Neuroscience.

[24]  L. Venance,et al.  Intercellular calcium signaling and gap junctional communication in astrocytes , 1998, Glia.

[25]  Hajime Takano,et al.  Micropatterned substrates: approach to probing intercellular communication pathways. , 2002, Analytical chemistry.

[26]  M. Norenberg,et al.  ATP-evoked calcium signal stimulates protein phosphorylation/dephosphorylation in astrocytes , 1991, Brain Research.

[27]  H. Kettenmann,et al.  Different Mechanisms Promote Astrocyte Ca2+ Waves and Spreading Depression in the Mouse Neocortex , 2003, The Journal of Neuroscience.

[28]  A. Moreno,et al.  Gap Junctions between Cells Expressing Connexin 43 or 32 Show Inverse Permselectivity to Adenosine and ATP* , 2002, The Journal of Biological Chemistry.

[29]  L. Venance,et al.  Control and Plasticity of Intercellular Calcium Waves in Astrocytes: A Modeling Approach , 2002, The Journal of Neuroscience.

[30]  M. Salter,et al.  ATP-evoked increases in intracellular calcium in neurons and glia from the dorsal spinal cord , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  M. Nedergaard,et al.  ATP-Mediated Glia Signaling , 2000, The Journal of Neuroscience.

[32]  M. Rathbone,et al.  Glial cells express multiple ATP binding cassette proteins which are involved in ATP release , 2002, Neuroreport.

[33]  A. Cornell-Bell,et al.  Glutamate‐induced calcium signaling in astrocytes , 1994, Glia.

[34]  J. Glowinski,et al.  Homotypic and Heterotypic Coupling Mediated by Gap Junctions During Glial Cell Differentiation In Vitro , 1995, The European journal of neuroscience.

[35]  R. Swanson,et al.  ATP‐induced ATP release from astrocytes , 2003, Journal of neurochemistry.

[36]  W. Gibson,et al.  Quantal and non-quantal current and potential fields around individual sympathetic varicosities on release of ATP. , 2001, Biophysical journal.

[37]  H. Kimelberg,et al.  Developmental expression of metabotropic P2Y1 and P2Y2 receptors in freshly isolated astrocytes from rat hippocampus , 2001, Journal of neurochemistry.

[38]  M. Matteoli,et al.  Nucleotide‐mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptors , 2003, Glia.

[39]  E. Newman,et al.  Propagation of Intercellular Calcium Waves in Retinal Astrocytes and Müller Cells , 2001, The Journal of Neuroscience.

[40]  M. Nedergaard,et al.  Cytoskeletal Assembly and ATP Release Regulate Astrocytic Calcium Signaling , 1998, The Journal of Neuroscience.

[41]  S. Ferroni,et al.  ATP‐induced, sustained calcium signalling in cultured rat cortical astrocytes: evidence for a non‐capacitative, P2X7‐like‐mediated calcium entry , 2003, FEBS letters.

[42]  S. B. Kater,et al.  An extracellular signaling component in propagation of astrocytic calcium waves. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[43]  A. Charles,et al.  Intercellular signaling in glial cells: Calcium waves and oscillations in response to mechanical stimulation and glutamate , 1991, Neuron.

[44]  Mark Ellisman,et al.  Protoplasmic Astrocytes in CA1 Stratum Radiatum Occupy Separate Anatomical Domains , 2002, The Journal of Neuroscience.

[45]  K. Willecke,et al.  Astrocyte cultures from conditional connexin43‐deficient mice , 2004, Glia.

[46]  N. Mori,et al.  Extracellular ATP-induced inward current in isolated epithelial cells of the endolymphatic sac. , 1999, Biochimica et biophysica acta.

[47]  M. Salter,et al.  P2Y1 Purinoceptor-Mediated Ca2+ Signaling and Ca2+ Wave Propagation in Dorsal Spinal Cord Astrocytes , 2000, The Journal of Neuroscience.

[48]  S. Koizumi,et al.  Spatial and temporal aspects of Ca2+ signaling mediated by P2Y receptors in cultured rat hippocampal astrocytes. , 2002, Life sciences.

[49]  A. Charles,et al.  Intercellular calcium waves in glia , 1998, Glia.

[50]  F. Sachs,et al.  Mechanically Induced Calcium Movements in Astrocytes, Bovine Aortic Endothelial Cells and C6 Glioma Cells , 2000, The Journal of Membrane Biology.

[51]  M. Salter,et al.  Differential Frequency Dependence of P2Y1- and P2Y2- Mediated Ca 2+ Signaling in Astrocytes , 2003, The Journal of Neuroscience.

[52]  J. Glowinski,et al.  Inhibition by anandamide of gap junctions and intercellular calcium signalling in striatal astrocytes , 1995, Nature.

[53]  Mitsunori Fukuda,et al.  Synaptotagmin IV regulates glial glutamate release. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[54]  M. Rathbone,et al.  Rat astroglial P2Z (P2X7) receptors regulate intracellular calcium and purine release. , 1996, Neuroreport.

[55]  G Burnstock,et al.  Receptors for purines and pyrimidines. , 1998, Pharmacological reviews.

[56]  B. J. Roth,et al.  A mathematical model of agonist-induced propagation of calcium waves in astrocytes. , 1995, Cell calcium.

[57]  Z Wang,et al.  Direct observation of calcium-independent intercellular ATP signaling in astrocytes. , 2000, Analytical chemistry.

[58]  E. Ito,et al.  Ca2+ signaling regulated by an ATP-dependent autocrine mechanism in astrocytes , 2001, Neuroreport.

[59]  W. Gibson,et al.  Quantal currents and potential in the three-dimensional anisotropic bidomain model of smooth muscle. , 1997, Bulletin of Mathematical Biology.

[60]  P. Magistretti,et al.  Astrocytes generate Na+-mediated metabolic waves. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[61]  C. Naus,et al.  Intercellular Calcium Signaling in Astrocytes via ATP Release through Connexin Hemichannels* , 2002, The Journal of Biological Chemistry.

[62]  Michael M. Halassa,et al.  Fusion-related Release of Glutamate from Astrocytes* , 2004, Journal of Biological Chemistry.

[63]  W. Gibson,et al.  Quantal transmission at purinergic junctions: stochastic interaction between ATP and its receptors. , 1995, Biophysical journal.

[64]  H. Muyderman,et al.  Modulation of mechanically induced calcium waves in hippocampal astroglial cells. Inhibitory effects of α 1-adrenergic stimulation , 1998, Brain Research.

[65]  G. Dubyak,et al.  Colocalization of ATP Release Sites and Ecto-ATPase Activity at the Extracellular Surface of Human Astrocytes* , 2003, Journal of Biological Chemistry.

[66]  D C Spray,et al.  Intercellular Communication in Spinal Cord Astrocytes: Fine Tuning between Gap Junctions and P2 Nucleotide Receptors in Calcium Wave Propagation , 2000, The Journal of Neuroscience.

[67]  J. Glowinski,et al.  Gap junctional communication and pharmacological heterogeneity in astrocytes cultured from the rat striatum , 1998, The Journal of physiology.