Fig. 2

Ionic flux. (A) K⁺ efflux: Detection of the elevated levels of ATP in the extracellular medium by P2 × 7R and activation of this receptor by caspase-4/5/11 results in the opening of the channel which induces K⁺ efflux. The decrease in intracellular potassium concentration activates the NLRP3 inflammasome. The binding of never-in-mitosis A-related kinase 7 (NEK7, a well‑conserved serine/threonine kinase also known as NIMA‑related kinase 7), to NLRP3 downstream to K⁺ efflux plays a key role in this process resulting in the molecular complex formation and further activating the NLRP3 inflammasome. Cell membrane destruction, some microbial toxins, and the non-canonical pathway also contribute to the NLRP3 inflammasome activation via K⁺ efflux. (B) Ca²⁺ mobilization: Calcium ion mobilization from the ER through Ca²⁺ channels or extracellular Ca²⁺ influx through the P2 × 7 receptor triggered by ATP results in increased intracellular Ca²⁺ levels. Ca²⁺ overload prompts the assembly of the NLRP3 inflammasome complex and plays an important role in the activation of the NLRP3 inflammasome. Ca²⁺ may facilitate the interaction between NLRP3 and ASC by inducing conformational changes