γ-AChR/ε-AChR switch at agrin-induced postsynaptic-like apparatus in skeletal muscle

Abstract

We transfected the extrajunctional region of denervated soleus muscles in adult rats with neural agrin cDNA to induce myofibers to form postsynaptic-like apparatus containing acetylcholine receptor (AChR) aggregates. By 1 week ~30% of the AChR aggregates contained a mixture of ε- AChRs and γ-AChRs while ~70% had only γ-AChRs. If the transfected muscles were reinnervated in the original junctional region, the postsynaptic-like apparatus, despite the absence of apposed axon terminals, gradually came to have only ε-AChRs. We conclude that at the postsynaptic apparatus of ectopic neuromuscular junctions formed by a foreign nerve implanted into the extrajunctional region of denervated muscles, agrin secreted by the axon terminal plays a direct role in the γ-AChR/ε-AChR switch that occurs as the apparatus reaches maturity. Our findings, together with results from other studies, indicate further that agrin and acetylcholine are the only nerve- derived factors required for this switch.