Microglial Ramification, Surveillance, and Interleukin-1β Release Are Regulated by the Two-Pore Domain K+ Channel THIK-1

摘要: Microglia exhibit two modes of motility: they constantly extend and retract their processes to survey the brain, but also send out targeted envelop sites tissue damage. We now show that these motility differ mechanistically. identify two-pore domain channel THIK-1 as main K+ expressed in microglia situ. is tonically active, its activity potentiated by P2Y12 receptors. Inhibiting function pharmacologically or gene knockout depolarizes microglia, which decreases microglial ramification thus reduces surveillance, whereas blocking receptors does not affect membrane potential, ramification, surveillance. In contrast, process outgrowth damaged requires receptor activation unaffected THIK-1. Block inhibits release pro-inflammatory cytokine interleukin-1β from activated consistent with loss being needed for inflammasome assembly. Thus, immune surveillance require activity.