Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptor

P2X(7) receptors are ATP-gated cation channels; their activation in macrophage also leads to rapid opening of a membrane pore permeable to dyes such as ethidium, and to release of the pro-inflammatory cytokine, interleukin-1 beta (IL-1 beta). It has not been known what this dye-uptake path is, or whether it is involved in downstream signalling to IL-1 beta release. Here, we identify pannexin-1, a recently described mammalian protein that functions as a hemi-channel when ectopically expressed, as this dye-uptake pathway and show that signalling through pannexin-1 is required for processing of caspase-1 and release of mature IL-1 beta induced by P2X(7) receptor activation.