Shown is a representation of the muscle nAChR from the Torpedo sp. electric organ based on the electron microscopy reconstructions of Unwin (13). The pentameric structure in Torpedo and mammalian skeletal muscle consists of two copies of an α subunit, one β, one δ, and one γ or ε, depending on whether the muscle receptor is innervated. The portion between the two parallel dark gray sheets represents the transmembrane span. Acetylcholine binds cooperatively at the α-γ and α-δ subunit interfaces, as shown by the radial entry of the blue arrow, causing the channel gate, located in the transmembrane span, to open. Ion entry is shown by the gray arrow leading into a central vestibule of the channel surrounded by the five subunits. The structure is based on ref. 14 (Protein Data Bank [PDB] 2BG9). The insets show ribbon diagrams of portions of the α subunit where the two mutations, G74C and V188M, reside. Also shown in the lower inset in white, with red denoting oxygen and blue nitrogen, are the aromatic side chains Y190 and Y93 and charged side chains D200 and K145, forming the proposed tetrad of interacting side chains involved in activation (1). The diagrams are based on a crystal structure of the α1 subunit from mouse complexed with the snake toxin α-bungarotoxin (ref. 15; PDB 2QC1). The toxin structure has been removed for clarity.