Schematic diagrams showing (upper) transmembrane topology of nAChR subunits and (lower) features of nAChR subunit assembly. Upper schematic illustrates the existence of an extensive, extracellular N-terminal region, four transmembrane segments, a cytoplasmic loop, and an extracellular C terminus for each nACh receptor subunit (not drawn to scale; surrounding lipid bilayer is also represented schematically). Lower schematic illustrates known arrangements of subunits constituting a nACh receptor type predominant in fetal skeletal muscle (left) and constituting a homooligomeric nACh receptor composed of α7 subunits (right). Assembly of subunits is thought to be regulated and limited by interactions between amino acid residues at subunit interfaces. Ligand binding pockets are thought to be formed at a subset of these assembly interfaces. For example, two distinct classes of ligand binding sites are formed at interfaces between α1 and γ subunits or between α1 and δ subunits of the nACh receptor from fetal muscle. Five largely similar ligand binding domains are thought to be formed at negative and positive faces of α7 subunits in homooligomeric α7-nACh receptors. All subunits contribute to channel formation, reflected by influences of every nACh receptor subunit identified to date on features of channel activity upon interaction with nicotinic ligand (see Table 1).