Figure 1.

Basic structure of connexin and pannexin-based channels. Connexins and pannexins share a similar membrane topology with four α-helical transmembrane domains connected by two extracellular loops and one cytoplasmic loop; both the amino- and carboxy-termini are intracellular. The relative positions of the extracellular loop cysteines (green balls) and glycosylated asparagines (blue branches) are also shown. Hemichannels (also known as connexons) are formed by the oligomerization of six subunit connexins around a central pore. Pannexons are single membrane channels that are composed of six pannexin subunits. Recently, a band pattern more consistent with an octamer than a hexamer was observed in Panx2 by cross-linking studies and native gels of purified homomeric full-length and C-terminal truncation mutants (Ambrosi et al., 2010). Under resting conditions, hemichannels and pannexons remain preferentially closed, but they may be activated by diverse physiological and pathological conditions and offer a diffuse transmembrane route between the intra- and extracellular milieu. Hemichannels dock each other to form functional cell-to-cell channels termed gap junction channels (GJCs). GJCs aggregate in well-known anatomical structures called gap junctions to facilitate the intercellular cytoplasmic exchange of metabolites, second messengers and ions.