The advent of multicellular organisms, some 800 million years ago, necessitated the development of mechanisms for cell-to-cell synchronization and for the spread of signals across increasingly large cell populations [168, 185]. Many structures and mechanisms have evolved to achieve such functions [4, 15]. Among these mechanisms, one which is prominent in both the invertebrate and the vertebrate world, across the entire phylogenetic scale, involves the transmembrane flux of large cytosolic and extracellular molecules [, , , , –71, 121, 128, 129, 147, 154, 163]. These fluxes, in turn, are dependent on the formation of specific channels that in all animal classes are made by tetra-span integral membrane proteins [, , –71, 121, 128, 129, 147, 154, 163] (Fig. 1).