title: Absence of nerve-dependent conversion of rapidly degrading to stable acetylcholine receptors at adult innervated endplates.
abstract: It has been suggested that acetylcholine receptors newly inserted into adult innervated endplates have a rapid degradation rate, but are normally converted to a stable, slowly degrading form in a nerve-dependent fashion. Denervation therefore should eliminate conversion and cause pre-existing unconverted receptors to continue degrading rapidly. We tested this model of nerve-dependent conversion in mouse sternomastoid muscle, using quantitative electron microscopic autoradiography in order to specifically examine degradation of receptors at identified endplate membrane. Prior to denervation, we labelled the receptors with sequential alpha-bungarotoxin exposures, using conditions designed to maximize the predicted effect of denervation. However, we observed no difference in the rate of receptor degradation at innervated and denervated endplates up to seven days after denervation (at which time accelerated degradation of pre-existing stabilized receptors is known to begin in this muscle). The regulation of endplate acetylcholine receptor metabolic turnover is a complex and still largely undefined issue, related to many factors such as subunit composition, cytoskeleton and basement membrane composition, muscle activity, and neural influences. In particular, the nerve's influence on the normal stabilization of receptors at innervated adult endplates has been controversial. Our data indicate that slow degradation is probably an inherent property of newly inserted junctional receptors, and argue against nerve-dependent conversion and stabilization. Based on the present data, however, we cannot rule out the presence of a small nerve-independent subpopulation that degrades rapidly. The molecular mechanisms involved in establishing and maintaining a stable population of adult endplate acetylcholine receptors remain to be established.
authors.affiliation: Section of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853-2702, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Stiles
authors.forename: M M
authors.initials: MM
authors.lastname: Salpeter
mesh_terms: D000818:Animals; D001345:Autoradiography; D002038:Bungarotoxins / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D005260:Female; D006651:Histocytochemistry; D051379:Mice; D008854:Microscopy, Electron; D009045:Motor Endplate / Q000378:metabolism* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000294:innervation; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013696:Temperature
chemical_list: D002038:Bungarotoxins; D018680:Cholinergic Antagonists; D011950:Receptors, Cholinergic