The Life History of Acetylcholine Receptors

The acetylcholine (ACh) receptor is the major integral membrane glycoprotein known to occur in the postsynaptic membrane at the neuromuscular junction. This chapter describes the life history of extra-junctional ACh receptor molecules. Average extra-junctional receptor lifetimes have been estimated as 8–30 h for ACh receptors in various muscles and muscle cultures from homeothermic species. For cultured chick and calf skeletal muscle in vitro, receptor lifetimes have been determined by pulse-chase experiments, involving direct labeling of receptor molecules with isotopically labelled amino acids. In other cases, estimates are based upon the loss of radioactivity from the muscle after iodinated α-bungarotoxin was bound to ACh receptor sites. The bound α-bungarotoxin may slightly decrease the turnover rate. Studies on the mechanism of degradation have involved labelling of receptor sites with iodinated a-bungarotoxin, and then following the fate of the radioactivity. The degradation process is energy dependent and not tightly coupled to receptor biosynthesis. α-Bungarotoxin receptor complexes are internalized and transported to secondary lysosomes where proteolysis occurs. The appearance of ACh hypersensitivity following denervation of adult skeletal muscle has been shown to result from turn-on of receptor biosynthesis.