Figure 1.

Model representing a putative mechanism of ATP-induced inflammasome activation. Low extracellular ATP concentration (<100 µM) selectively activates the more sensitive P2X4 receptor channel (i). Opening of the P2X4 channel leads to K⁺ efflux, with the subsequent increase in [K⁺]_o activating Panx1 (ii). Panx1 channel opening leads to the release of ATP, further activating P2X4 and P2X7 receptor channels (iii). Direct P2X7-mediated recruitment of Panx1 could also enhance such a positive feed-forward loop. P2X4, P2X7, and Panx1 would thereby all contribute to the assembly of the inflammasome complex via K⁺ efflux and to the consequent increase in [K⁺]_o and decrease in [K⁺]_i,. A direct interaction between Panx1 and inflammasome components may also occur. Depicted here is a putative mechanism for neuronal autocrine activation of the inflammasome; however, this amplification process could also participate in paracrine signaling as part of a neuron-to-immune cell cross talk.