Turnover of acetylcholine receptors at the endplate revisited: novel insights into nerve-dependent behavior.

Abstract

The turnover of nicotinic acetylcholine receptors (AChR) is a critical factor that determines function and safety of neuromuscular transmission at the nerve-muscle synapses, i.e. neuromuscular junctions (NMJs). Previously, three different populations of AChRs exhibiting distinct stereotypic and activity-dependent half-life values were observed in mouse muscles. To address AChR turnover in more detail, we here employed a recently developed longitudinal radioiodine assay that is based on repetitive measurements of radio emission from the same animals over long periods of time in combination with systematic variation of the time elapsed between AChR pulse-labeling and muscle denervation. Modeling of the data revealed profiles of AChR de novo synthesis and receptor incorporation into the postsynaptic membrane. Furthermore, decay of pre-existing AChRs upon denervation showed a peculiar pattern corroborating earlier findings of a two-step stabilization of AChRs.