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 P2X_4/7 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.