DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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CHAPTER 11
Figure 11–2. Subunit arrangement and molecular structure of the nicotinic acetylcholine receptor. A. Longitudinal view of receptor
schematic with the γ subunit removed. The remaining subunits, two copies of α, one of β, and one of δ, are shown to surround an internal
channel with an outer vestibule and its constriction located deep in the membrane bilayer region. Spans of α-helices with slightly
bowed structures form the perimeter of the channel and come from the TM2 region of the linear sequence (Figure 11–1). Acetylcholine
(ACh) binding sites, indicated by arrows, are found at the αγ and αδ (not visible) interfaces. B. Longitudinal view of the receptor from
Torpedo showing secondary structure and membrane topology from 4 Å electron micrograph data (Unwin, 2005). The ACh binding
protein (panel C) is homologous to the extracellular domain of the nicotinic receptor (Figure 11–1). The protein is a homopentamer
that binds nicotinic receptor ligands with the expected selectivity and, when fused to the TM portions of the receptor, yields a functional
ligand-gated channel. The subunit structure of the ACh binding protein is clear from the top view (panel C, upper orientation)
and side view (panel C, lower orientation). The agonist nicotine is shown bound to the ACh binding protein with its atoms modeled
as spheres in C. Nicotinic receptor subunit arrangement is shown in D, with examples of subunit assembly and location of agonist binding
sites (small red circles) at α subunit-containing interfaces in nicotinic receptors. A total of 17 functional receptor isoforms have
been observed in vivo, with different ligand specificity, relative Ca 2+ /Na + permeability, and physiological function as determined by
their subunit composition. The only isoform found at the neuromuscular junction (and in the electric organ of Torpedo) is that shown
here. The 16 neuronal receptor isoforms, found at autonomic ganglia and in the central nervous system, form homo- and heteropentameric
nicotinic receptors composed of α2-α10 and β2-β4 subunits.
AGENTS ACTING AT THE NEUROMUSCULAR JUNCTION AND AUTONOMIC GANGLIA