The Molecular Neurobiology of the Acetylcholine Receptor

Abstract

The acetylcholine receptor (AChR) is the most thoroughly characterized component ofthe neuromuscular transduction process. Earlier reviews that summarize the structural and biochemical features of the AChR include Popot & Changeux (1984), Stroud (1983), Conti-Tronconi & Raftery (1982), and Karlin (1980). This receptor translates the binding of the neurotrans­ mitter, acetylcholine (ACh), into a rapid increase and subsequent decrease in the permeability of the endplate membrane to the passage of cations. Inward flux of ions through the channel is passive, driven by elec­ trochemical gradients across the receptor-containing membrane. The physiological effect is to temporarily depolarize the endplate, a response that is translated into muscular contraction in the case of a neuromuscular junction, or potentiation of electric tissue in the stacked asymmetric cells of electric organs in Torpedo (a marine elasmobranch) or Electrophorus (a freshwater teleost). The availability of acetylcholine receptors from electric tissue was a fundamental key to molecular characterization. The subunit stoichiometry of the four identified polypeptides has been unequivocally established as 1X2/3yb, and the funnel shape of the molecule has been well characterized with respect to position of the ion channel. Distribution of protein relative to the phospholipid bilayer and some aspects ofthe subunit arrangements in a quasipentameric structure around the ion channel have also been established. The genes for the four subunits that constitute the