Fig. 6: Squaramides decrease intracellular potassium concentration.
From: Squaramides enhance NLRP3 inflammasome activation by lowering intracellular potassium
A LPS-primed (1 μg/mL; 4 h) BMDMs were treated with 10 μM NVR compound or vehicle control (DMSO 0.5% v/v) in conjunction with 10 μM nigericin or vehicle control (EtOH 0.5% v/v) for 15 min. Intracellular potassium content was determined by ICP-MS from frozen cell pellets. Data correspond to 6 biological repeats. Differences to a theoretical mean of 100 were assessed by multiple t-tests and corrected for multiple comparisons with Holm-Sidak method. *p < 0.05, **p < 0.01, ****p < 0.0001. B Modelled structure of NVR77 in complex with potassium (purple) and chloride (green). See also Figs. S6 and S7, and Supplementary information for details of modelling parameters. C Table illustrating the binding energies for the NVR77:Chloride:Sodium complex when considering the relative abundance of sodium and potassium. D LPS-primed (1 μg/mL; 4 h) BMDMs were treated with 10 μM NVR compound or vehicle control (DMSO 0.5% v/v) for 15 min before addition of nigericin (1–10 μM) or vehicle control (EtOH 0.5% v/v). After 90 minutes, culture supernatant was recovered and assessed for IL-1β content by ELISA. Data correspond to mean +/− SD of 4 biological repeats. Differences assessed by Two-way ANOVA with Dunnett’s post test. *p < 0.05, **p < 0.01 Hashtags denote differences with vehicle control. ###p < 0.001.
