Functional role of calcium signals for microglial function

In this review we summarize mechanisms of Ca2+ signaling in microglial cells and the impact of Ca2+ signaling and Ca2+ levels on microglial function. So far, Ca2+ signaling has been only characterized in cultured microglia and thus these data refer rather to activated microglia as observed in pathology when compared with the resting form found under physiological conditions. Purinergic receptors are the most prominently expressed ligand-gated Ca2+-permeable channels in microglia and control several microglial functions such as cytokine release in a Ca2+-dependent fashion. A large variety of metabotropic receptors are linked to Ca2+ release from intracellular stores. Depletion of these intracellular stores triggers a capacitative Ca2+ entry. While microglia are already in an activated state in culture, they can be further activated, for example, by exposure to bacterial endotoxin. This activation leads to a chronic increase of [Ca2+](i) and this Ca2+ increase is a prerequisite for the release of nitric oxide and cytokines. Moreover, several factors (TNF alpha, IL-1 beta, and IFN-gamma) regulate resting [Ca2+], levels. (c) 2006 Wiley-Liss, Inc.