Brain extract causes acetylcholine receptor redistribution which mimics some early events at developing neuromuscular junctions.

Abstract

The effect of rat brain extract on rat muscle cells in vitro by light microscope and EM autoradiography after labeling acetylcholine receptors (AChR) with 125I-.alpha.-bungarotoxin was studied. In the absence of brain extract, peak site densities within AChR clusters usually do not exceed 4000 sites/.mu.m2. Within hours after exposure to brain extract, AChR redistribute to form clusters in which the peak site densities are > 10,000 sites/.mu.m2. Receptor concentration within extract-induced clusters is within a factor of 2 of that at the neuromuscular junction (nmj). In the absence of extract, the AChR and AChR clusters are predominantly on the bottom surface of the myotubes (facing the tissue culture dish). After extract treatment, they are predominantly at the top surface. Plasma membrane in regions of high-density AChR clusters is enriched in membrane with enhanced electron density and surface basal lamina whether or not cells are treated with extract. Extract causes an increase in both these specializations on the top surface of the myotubes. Brain extract does not produce an overall increase in AChR site density or a marked change in degradation rate of receptors in either clustered or nonclustered regions. By producing AChR clusters with junctional site densities and enhanced surface specialization, and by causing an overall shift in AChR distribution, brain extract mimics early events reported at developing nmj.