title: Calcium influx through reversed NCX controls migration of microglia.
abstract: Microglia, the immune cells of the central nervous system (CNS), are busy and vigilant guards of the adult brain, which scan brain parenchyma for damage and activate in response to lesions. Release of danger signals/chemoattractants at the site of damage initiates microglial activation and stimulates migration. The main candidate for a chemoattractant sensed by microglia is adenosine triphosphate (ATP); however, many other substances can have similar effects. Some neuropeptides such as angiotensin II, bradykinin, endothelin, galanin and neurotensin are also chemoattractants for microglia. Among them, bradykinin increases microglial migration using mechanism distinct from that of ATP. Bradykinin-induced migration is controlled by a G(i/o)-protein-independent pathway, while ATP-induced migration involves G(i/o) proteins as well as mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)-dependent pathway. Galanin was reported to share certain signalling cascades with bradykinin; however, this overlap is only partial. Bradykinin, for example, stimulates Ca(2+) influx through the reversed Na(+)/Ca(2+) exchange (NCX), whereas galanin induces intracellular Ca(2+) mobilization by inositol-3,4,5-trisphosphate (InsP(3))-dependent Ca(2+) release from the intracellular store. These differences in signal cascades indicate that different chemoattractants such as ATP, bradykinin and galanin control distinct microglial functions in pathological conditions such as lesion and inflammation and NCX contributes to a special case of microglial migration.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. noda@phar.kyushu-u.ac.jp
authors.forename: Mami
authors.initials: M
authors.lastname: Noda
authors.forename: Masataka
authors.initials: M
authors.lastname: Ifuku
authors.forename: Yuki
authors.initials: Y
authors.lastname: Mori
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D017628:Microglia / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D009479:Neuropeptides; D018129:Phosphatidylinositol Phosphates; D019831:Sodium-Calcium Exchanger; C060974:phosphatidylinositol 3,4,5-triphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium