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.