A General Treatment of Ligand Binding to the Acetylcholine Receptor

Abstract

The nicotinic acetylcholine receptor is a membrane-bound macromolecule which contains both, the binding sites for acetylcholine and an acetylcholine controlled cation channel (For review see: Maelicke 1984, Changeux et al. 1984). When plotted versus the agonist concentration, the response (depolarisation of the membrane) follows a sigmoid curve. Half-maximal response is observed at 28μM acetylcholine (Dreyer et al. 1978), whereas equilibrium binding studies yield Kd1 = 25 nM and Kd2 =8 nM for two classes of sites (Fels et al. 1982). The large discrepancy (three orders of magnitude) in the results of both types of experiments may be attributed to a conformational change of the receptor at prolonged exposure to agonists (desensitisation).