Schematic depiction of the extracellular domains of a Cx26 hemichannel. The box in the left panel shows the region depicted in detail on the right. The front three connexin subunits are not shown. Each subunit is represented by a different color. Cylinders inside the subunits represent the transmembrane domains. TM1 denotes the first transmembrane domain, which is exposed to the pore lumen. E1 and E2 denote the first and second extracellular loop domains, respectively. The parahelix region mentioned in the text corresponds to residues 43–51, comprising the uppermost residues of TM1 and the contiguous residues with white labels in E1. The illustration is not drawn to scale or strictly according to the atomic structure (from Sanchez et al. [2013]).