Muscle activity-resistant acetylcholine receptor accumulation is induced in places of former motor endplates in ectopically innervated regenerating rat muscles

Expression of acetylcholine receptors (AChRs) in the extrajunctional muscle regions, but not in the neuromuscular junctions, is repressed by propagate d electric activity in muscle fibers. During regeneration, subsynaptic-like specializations accumulating AChRs are induced in new myotubes by agrin at tached to the synaptic basal lamina at the places or former motor endplates even in the absence of innervation. We examined whether AChRs still accumu lated at these places when the regenerating muscles were ectopically innerv ated and the former synaptic places became extrajunctional. Rat soleus musc les were injured by bupivacaine and ischemia to produce complete myofiber d egeneration. The soleus muscle nerve was permanently severed and the muscle was ectopically innervated by the peroneal nerve a few millimeters away fr om the former junctional region. After 4 weeks of regeneration. the muscles contracted upon nerve stimulation, showed little atrophy and the cross-sec tion areas of their fibers were completely above the range in non-innervate d regenerating muscles, indicating successful innervation. Subsynaptic-like specializations in the former junctional region still accumulated AChRs (a nd acetylcholinesterase) although no motor nerve endings were observed in t heir vicinity and the cross-section area of their fibers clearly demonstrat ed that they were ectopically innervated. We conclude that the expression o f AChRs at the places of the former neuromuscular junctions in the ectopica lly innervated regenerated soleus muscles is activity-independent. (C) 2001 ISDN. Published by Elsevier Science Ltd. All rights reserved.