Gap junctions are usually found in clusters and enable intercellular communication by allowing the passage of small molecules between cells¹. They play important roles in different biological processes. These include differentiation, cell cycle synchronization, cellular development, neuronal activity and the immune response^2-4.

Proteins involved in gap junction formation are composed of four transmembrane domains, two extracellular loops and one intracellular loop and intracellular N- and C-termini^5,6. Several consensus cysteine residues are in the extracellular loop and are essential and necessary for intercellular docking of gap junction hemichannels in the opposing cell membrane^5-7.

Pannexins (Pannexin 1, Pannexin 2 and Pannexin 3) belong to the superfamily of gap junction proteins. Pannexin 1 (PANX1) is ubiquitously expressed, Pannexin 2 (PANX2) is specifically expressed in the human brain and widespread in rodents and Pannexin 3 (PANX3) is also detected in the brain⁸.

The gating properties of Pannexins were studied in Xenopus oocytes and results demonstrate that only PANX1 is able to form homomeric hemichannels, and is also able to form heteromeric hemichannels with PANX2 but not with PANX3^9,10. Not surprising, PANX1 gating properties depend whether it forms homomeric or heteromeric hemichannels.

A number of different stimuli are known to open these channels and include mechanical stress, extracellular ATP, increases in intracellular Ca²⁺ and inflammation⁹.

Possible roles for Pannexins include paracrine signaling in vascular endothelial cells and taste cell signaling⁹. Pannexin-1 was shown to interact with NMDA receptors in epilepsy, ischemia, pain and other pathologies¹⁰.