Calcium Signalling in Microglia

Intracellular Ca2+ signalling represents the substrate of microglial excitability. Spatially and temporally organised changes in the free cytoplasmic Ca2+ concentration ([Ca2+]i) are generated in response to physiological and pathological stimuli. Parameters of these intracellular Ca2+ signals are defined by Ca2+ signalling toolkits that may change with age or context therefore increasing adaptive capabilities of microglia. Main Ca2+ signalling pathways in microglial cells are associated with dynamic endoplasmic reticulum Ca2+ stores and with plasmalemmal Ca2+ entry mediated by several sets of Ca2+-permeable channels including transient receptor potential (TRP) channels, ORAI channels and P2X4/7 purinoceptors. Microglial Ca2+ dynamics is also linked to TREM2 signalling cascade, contributing to neuroprotection in neurodegenerative diseases. Microglial Ca2+ signals act as reliable and precise sensors of brain dyshomeostasis and pathological insults.