Fig. 4

Elevated extracellular K⁺ inhibits NLRP3 inflammasome activation in THP-1 cells and primary human and mouse microglia. a Canonical inflammasome activation is blocked in THP-1 cells with a range of extracellular K⁺ concentrations (130–50 mM). Representative experiment. b 130 mM extracellular K⁺ blocks canonical inflammasome activation in primary human microglia. Representative experiment. c 130 mM extracellular K⁺ is non-toxic to THP-1 cells upon short-term (4 h) exposure. Representative experiment. d, e Overnight exposure of THP-1 cells to 130 mM extracellular K⁺ does not affect plasma membrane integrity (d) but does affect metabolic function (e), suggesting cytotoxicity at this timepoint, whereas 65 mM K⁺ has little effect by either measure. Representative experiments. f Both LPS- and α-syn-mediated IL-1β production by THP-1 cells are inhibited by 30 or 60 mM extracellular K⁺. 2 experiments, n = 3. g Both LPS-and α-syn-mediated IL-1β production by primary human microglia are also blocked by 60 mM extracellular K⁺. 2 experiments, n = 3. h Both 1 mM DA and 60 mM extracellular K⁺ inhibited IL-1β production induced by overnight treatment of primary mouse microglia with 10 µM α-syn. ***p < 0.001 by two-way ANOVA with Bonferroni multiple testing correction