Fig. 1.

Trafficking and regulated gating of connexin or pannexin hemichannels. The biosynthesis and trafficking of connexons or pannexons can result in nonjunctional hemichannels in the plasma membrane or further assembly into gap junctional complexes at sites of cell-to-cell contact. Multiple extracellular and intracellular stimuli have been implicated in the gating of nonjunctional hemichannels to the open state. These channels are permeable to both ions and small organic molecules, such as intracellular ATP or extracellular fluorescent dyes. The gating of hemichannels can be triggered by extracellular nucleotides that target various P2X or P2Y receptor subtypes. This can initiate a positive-feedback cycle of ATP-induced ATP release. However, the studies described by Qui and Dahl in this issue of AJP-Cell suggest that the released extracellular ATP can exert a negative allosteric action on pannexin-1-based hemichannels and thus dampen this positive-feedback cycle.