Morphological profile determines the frequency of spontaneous calcium events in astrocytic processes

Astrocytes express a complex repertoire of intracellular Ca 2+ transients (events) that represent a major form of signaling within individual cells and in the astrocytic syncytium. These events have different spatiotemporal profiles, which are modulated by neuronal activity. Spontaneous Ca 2+ events appear more frequently in distal astrocytic processes and independently from each other. However, little is known about the mechanisms underlying such subcellular distribution of the Ca 2+ events. Here we identify the initiation points of the Ca 2+ events within the territory of single astrocytes expressing genetically encoded Ca 2+ indicator GCaMP2 in culture or in hippocampal slices. We found that most of the Ca 2+ events start in thin distal processes. Our mathematical model demonstrated that a high surface-to-volume (SVR) of the thin processes leads to increased amplitude of baseline Ca 2+ fluctuations caused by a stochastic opening of Ca 2+ channels in the plasma membrane. Suprathreshold fluctuations trigger Ca 2+ -induced Ca 2+ release (CICR) from the Ca 2+ stores by activating inositol 1,4,5-trisphosphate (IP 3 ) receptors. In agreement with the model prediction, the spontaneous Ca 2+ events frequency depended on the extracellular Ca 2+ concentration. Astrocytic depolarization by high extracellular K + increased the frequency of the Ca 2+ events through activation of voltage-gated Ca 2+ channels (VGCC) in cultured astrocytes. Our results suggest that the morphological profile of the astrocytic processes is responsible for tuning of the Ca 2+ event frequency. Therefore, the structural plasticity of astrocytic processes can be directly translated into changes in astrocytic Ca 2+ signaling. This may be important for both physiological and pathological astrocyte remodeling. Main points Majority of spontaneous Ca 2+ events start in thin astrocytic processes Higher surface-to-volume ratio of the process is responsible for larger intracellular Ca 2+ fluctuations Larger intracellular Ca 2+ fluctuations trigger Ca 2+ -dependent Ca 2+ release