Muscle endplate nicotinic AChR. The nicotinic AChR of skeletal muscle is a pentameric channel complex consisting of 2 α subunits and 1 β, 1 γ, and 1 δ subunit in fetal and denervated muscle, and 2 α subunits and 1 β, 1 δ, and 1 ε subunit in adult muscle. All subunits have a similar structure with 4 transmembrane segments, M1 to M4. They form a channel complex with each subunit contributing equally to the ion-conducting central pore formed by the M2 segments. The pore is permeable to cations. The binding site for ACh is located in the long extracellular loop of the α subunit. The 3 main conformational states of the ligand-gated channels are closed, open, and desensitized. Binding of the transmitter opens the channel from the closed state, and, during constant presence of the transmitter, desensitization occurs. Only after removal of the transmitter, the channel can recover from desensitization and subsequently will be available for another opening. Mutations associated with subtypes of CMSs are indicated by conventional 1-letter abbreviations for the replaced amino acids.