Calcium Signalling in Microglia.

Intracellular Ca signalling represents the substrate of microglial excitability. Spatially and temporally organised changes in the free cytoplasmic Ca concentration ([Ca]) are generated in response to physiological and pathological stimuli. Parameters of these intracellular Ca signals are defined by Ca signalling toolkits that may change with age or context therefore increasing adaptive capabilities of microglia. Main Ca signalling pathways in microglial cells are associated with dynamic endoplasmic reticulum Ca stores and with plasmalemmal Ca entry mediated by several sets of Ca-permeable channels including transient receptor potential (TRP) channels, ORAI channels and P2X purinoceptors. Microglial Ca dynamics is also linked to TREM2 signalling cascade, contributing to neuroprotection in neurodegenerative diseases. Microglial Ca signals act as reliable and precise sensors of brain dyshomeostasis and pathological insults.