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The Journal of Neuroscience, June 15, 2002, 22(12):4850-4859
Control and Plasticity of Intercellular Calcium Waves in Astrocytes: A Modeling Approach
Thomas Höfer1, Laurent Venance2, and Christian Giaume2 1 Theoretische Biophysik, Institut für Biologie, Humboldt-Universität Berlin, 10115 Berlin, Germany, and 2 Institut National de la Santé et de la Recherche Médicale U114, Collège de France, 75231 Paris Cedex 05, France
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.
Key words: intercellular calcium waves; glial cells; inositol 1,4,5-trisphosphate; phospholipase C; gap junctions; mathematical model
Copyright © 2002 Society for Neuroscience 0270-6474/02/22124850-10$05.00/0
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