Figure 2.

(1) Extracellular ATP stimulation to the activation of PLC and the formation of IP₃, which, upon binding to ER receptors, promotes the release of Ca²⁺ stored in the ER. IP₃ and Ca²⁺ diffuse to adjacent cells through GJC, resulting in the diffusion of intracellular Ca²⁺ waves. (2) Extracellular ATP leads to the entry of extracellular Ca²⁺ into the cell by activating membrane P₂X receptors. (3) Activation of P₂Y receptors by ATP leads to PLC activation and IP₃ formation. Increased Ca²⁺ waves are induced by IP₃ and P₂X receptor opening, promoting ATP release through Cx43 HC, and extending Ca²⁺ waves to neighboring cells. (4) Astrocyte ATP release induces intraneuronal Ca²⁺ waves. Astrocyte HCs release ATP into the extracellular space, creating an ATP concentration gradient that triggers microglia activation. Extracellular ATP induces the microglia to release endogenous ATP that attracts distant microglia and promotes the inflammatory cascade. ATP, adenosine triphosphate; PLC, phospholipase C; IP₃, 1,4,5-trisphosphate receptor; ER, endoplasmic reticulum; GPCR, G-protein-coupled receptors; GJC, gap junction channel; HC, hemichannel.