Spatial separation of two different pathways accounting for the generation of calcium signals in astrocytes

Astrocytes integrate and process synaptic information and exhibit calcium (Ca 2+ ) signals in response to incoming information from neighboring synapses. The generation of Ca 2+ signals is mostly attributed to Ca 2+ release from internal Ca 2+ stores evoked by an elevated metabotropic glutamate receptor (mGluR) activity. Different experimental results associated the generation of Ca 2+ signals to the activity of the glutamate transporter (GluT). The GluT itself does not influence the intracellular Ca 2+ concentration, but it indirectly activates Ca 2+ entry over the membrane. A closer look into Ca 2+ signaling in different astrocytic compartments revealed a spatial separation of those two pathways. Ca 2+ signals in the soma are mainly generated by Ca 2+ release from internal Ca 2+ stores (mGluR-dependent pathway). In astrocytic compartments close to the synapse most Ca 2+ signals are evoked by Ca 2+ entry over the plasma membrane (GluT-dependent pathway). This assumption is supported by the finding, that the volume ratio between the internal Ca 2+ store and the intracellular space decreases from the soma towards the synapse. We extended a model for mGluR-dependent Ca 2+ signals in astrocytes with the GluT-dependent pathway. Additionally, we included the volume ratio between the internal Ca 2+ store and the intracellular compartment into the model in order to analyze Ca 2+ 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 Ca 2+ 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 Ca 2+ signal.