Neural agrin controls acetylcholine receptor stability in skeletal muscle fibers

At mammalian neuromuscular junctions (NMJs), innervation induces and mainta ins the metabolic stability of acetylcholine receptors (AChRs). To explore whether neural agrin may cause similar receptor stabilization, we injected neural agrin cDNA of increasing transfection efficiencies into denervated a dult rat soleus (SOL) muscles. As the efficiency increased, the amount of r ecombinant neural agrin expressed in the muscles also increased. This agrin aggregated AChRs on muscle fibers, whose half-life increased in a dose-dep endent way from 1 to 10 days. Electrical muscle stimulation enhanced the st ability of AChRs with short half-lives. Therefore, neural agrin can stabili ze aggregated AChRs in a concentration- and activity-dependent way. However , there was no effect of stimulation on AChRs with a long half-life (10 day s). Thus, at sufficiently high concentrations, neural agrin alone can stabi lize AChRs to levels characteristic of innervated NMJs.