title: Spatial separation of two different pathways accounting for the generation of calcium signals in astrocytes.
abstract: Astrocytes integrate and process synaptic information and exhibit calcium (Ca2+) signals in response to incoming information from neighboring synapses. The generation of Ca2+ signals is mostly attributed to Ca2+ release from internal Ca2+ stores evoked by an elevated metabotropic glutamate receptor (mGluR) activity. Different experimental results associated the generation of Ca2+ signals to the activity of the glutamate transporter (GluT). The GluT itself does not influence the intracellular Ca2+ concentration, but it indirectly activates Ca2+ entry over the membrane. A closer look into Ca2+ signaling in different astrocytic compartments revealed a spatial separation of those two pathways. Ca2+ signals in the soma are mainly generated by Ca2+ release from internal Ca2+ stores (mGluR-dependent pathway). In astrocytic compartments close to the synapse most Ca2+ signals are evoked by Ca2+ entry over the plasma membrane (GluT-dependent pathway). This assumption is supported by the finding, that the volume ratio between the internal Ca2+ store and the intracellular space decreases from the soma towards the synapse. We extended a model for mGluR-dependent Ca2+ signals in astrocytes with the GluT-dependent pathway. Additionally, we included the volume ratio between the internal Ca2+ store and the intracellular compartment into the model in order to analyze Ca2+ signals either in the soma or close to the synapse. Our model results confirm the spatial separation of the mGluR- and GluT-dependent pathways along the astrocytic process. The model allows to study the binary Ca2+ response during a block of either of both pathways. Moreover, the model contributes to a better understanding of the impact of channel densities on the interaction of both pathways and on the Ca2+ signal.
authors.affiliation: Technische Universität Berlin, Neural Information Processing Group, Berlin, Germany.|Bernstein Center for Computational Neuroscience, Berlin, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Oschmann
authors.affiliation: Technische Universität Berlin, Neural Information Processing Group, Berlin, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Mergenthaler
authors.affiliation: Technische Universität Berlin, Neural Information Processing Group, Berlin, Germany.
authors.forename: Evelyn
authors.identifier: 0000-0003-4103-068X
authors.initials: E
authors.lastname: Jungnickel
authors.affiliation: Technische Universität Berlin, Neural Information Processing Group, Berlin, Germany.|Bernstein Center for Computational Neuroscience, Berlin, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Obermayer
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D006801:Humans; D064688:Metabolic Flux Analysis / Q000379:methods; D008954:Models, Biological; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D062211:Spatio-Temporal Analysis
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D018094:Receptors, Metabotropic Glutamate; D002118:Calcium