Insertion of a connexon into the cell membrane results in the formation of a hemi-channel. This channel permits direct exchanges between cell cytoplasm and extracellular matrix (Figure 3). Freeze-fracture electron microscopy studies have revealed that cytoplasmic vesicles can fuse with the plasma membrane to permit connexon insertion (Shivers and Bowman 1985). Hemi-channels appear to play a role in isosmotic cell volume regulation (Quist et al., 2000), in apoptosis regulation (Contreras et al. 2002; John et al. 1999), and in the differentiation of different cell types (Boucher and Bennett 2003). Individual connexons have been observed dispersed around gap junction plaques. This observation suggests that there is a pool of connexons dispersed in the plasma membrane which can migrate to gap junction plaques (Benedetti et al. 2000; Hulser et al. 1997; Lauf et al. 2002; Gaietta et al. 2002).