title: Control and plasticity of intercellular calcium waves in astrocytes: a modeling approach.
abstract: Intercellular Ca2+ waves in astrocytes are thought to serve as a pathway of long-range signaling. The waves can propagate by the diffusion of molecules through gap junctions and across the extracellular space. In rat striatal astrocytes, the gap-junctional route was shown to be dominant. To analyze the interplay of the processes involved in wave propagation, a mathematical model of this system has been developed. The kinetic description of Ca2+ signaling within a single cell accounts for inositol 1,4,5-trisphosphate (IP3) generation, including its activation by cytoplasmic Ca2+, IP3-induced Ca2+ liberation from intracellular stores and various other Ca2+ transports, and cytoplasmic diffusion of IP3 and Ca2+. When cells are coupled by gap junction channels in a two-dimensional array, IP3 generation in one cell triggers Ca2+ waves propagating across some tens of cells. The spatial range of wave propagation is limited, yet depends sensitively on the Ca2+-mediated regeneration of the IP3 signal. Accordingly, the term "limited regenerative signaling" is proposed. The gap-junctional permeability for IP3 is the crucial permissive factor for wave propagation, and heterogeneity of gap-junctional coupling yields preferential pathways of wave propagation. Processes involved in both signal initiation (activation of IP3 production caused by receptor agonist) and regeneration (activation of IP3 production by Ca2+, loading of the Ca2+ stores) are found to exert the main control on the wave range. The refractory period of signaling strongly depends on the refilling kinetics of the Ca2+ stores. Thus the model identifies multiple steps that may be involved in the regulation of this intercellular signaling pathway.
authors.affiliation: Theoretische Biophysik, Institut für Biologie, Humboldt-Universität Berlin, 10115 Berlin, Germany. thomas.hoefer@rz.hu-berlin.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfer
authors.forename: Laurent
authors.initials: L
authors.lastname: Venance
authors.forename: Christian
authors.initials: C
authors.lastname: Giaume
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism*; D020013:Calcium Signaling; D002463:Cell Membrane Permeability; D003593:Cytoplasm / Q000378:metabolism; D017629:Gap Junctions; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D017136:Ion Transport; D007700:Kinetics; D008959:Models, Neurological; D008962:Models, Theoretical; D009473:Neuronal Plasticity; D051381:Rats; D011956:Receptors, Cell Surface / Q000819:agonists; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D011956:Receptors, Cell Surface; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases