Figure 13-1 Subunit composition of the nicotinic acetylcholine receptor (nAChR) in the end-plate surface of adult mammalian muscle. The adult AChR is an intrinsic membrane protein with five distinct subunits (α₂ βδepsilon). Each subunit contains four helical domains labeled M1 to M4. The M2 domain forms the channel pore. The upper panel shows a single α-subunit with its N and C termini on the extracellular surface of the membrane lipid bilayer. Between the N and C termini, the α-subunit forms four helices (M1, M2, M3, and M4) that span the membrane bilayer. The lower panel shows the pentameric structure of the nAChR of adult mammalian muscle. The N termini of two subunits cooperate to form two distinct binding pockets for acetylcholine (ACh). These pockets occur at the epsilon-α and the δ-α subunit interface. The M2 membrane-spanning domain of each subunit lines the ion channel. The doubly liganded ion channel has permeability equal to that of Na⁺ and K⁺ ; Ca²⁺ contributes approximately 2.5% to the total permeability. (Redrawn from Naguib M, Flood P, McArdle JJ, et al: Advances in neurobiology of the neuromuscular junction: Implications for the anesthesiologist. Anesthesiology 96:202–231, 2002.)