Fig. 1. Molecular architecture of connexin and pannexin (hemi)channels and gap junctions.

Connexins and pannexins consist of four membrane-spanning domains, two extracellular loops, one cytoplasmic loop, and cytoplasmic N-terminal tail and C-terminal tail. Connexins contain three cysteine residues in their extracellular loops, while pannexins only have two. Unlike connexins, pannexins may be N-glycosylated on their extracellular loops. 6 connexin proteins are able to form a hemichannel, while pannexins form a connexin-hemichannel-like channel, composed of six or eight pannexin proteins. Gap junctions are specialized regions of the plasma membrane that form juxtaposed connexons or hemichannels, composed only of connexins, between two adjacent cells. Gap junctions allow the intercellular diffusion of small molecules, metabolites and secondary messengers, a flux called GJIC.