Ligand-induced conformation changes in Torpedo californica membrane-bound acetylcholine receptor

Abstract

A time-dependent increase in ligand affinity was studied in cholinergic ligand binding to T. californica acetylcholine receptor by inhibition of the kinetics of [125I]-.alpha.-bungarotoxin-receptor complex formation. The conversion of the acetylcholine receptor from low to high affinity form was induced by agonists and antagonists of acetylcholine and was reversible on removal of the ligand. The slow ligand induced affinity change in vitro resembled electrophysiological desensitization observed at the neuromuscular junction and described by a 2-state model. A quantitative treatment of the rate and equilibrium constants determined for binding of the agonist carbamoylcholine to membrane bound acetylcholine receptor indicated that the 2-state model is not compatible with the in vitro results.