Motor nerve terminal outgrowth and acetylcholine receptors: inhibition of terminal outgrowth by alpha-bungarotoxin and anti-acetylcholine receptor antibody.

Motor nerves undergo extensive terminal outgrowth when the muscles they supply are "functionally denervated." In this study, we have investigated the role of the acetylcholine receptors (AChRs), newly appearing in such muscles, in promoting nerve terminal outgrowth. The amount of outgrowth was determined by morphometric measurement of nerve terminal branching, endplate length, and ultraterminal sprouts, in cholinesterase-silver-stained neuromuscular junctions. Presynaptic neuromuscular blockade with botulinum toxin induced pronounced nerve terminal outgrowth in both the rat and mouse soleus muscles, although ultraterminal sprouts did not occur in the rat soleus. By contrast, postsynaptic neuromuscular blockade with alpha-bungarotoxin (alpha-BuTx) induced little or no terminal outgrowth, although it caused "functional denervation." Moreover, alpha-BuTx and anti-AChR antibody inhibited the terminal outgrowth otherwise induced by botulinum toxin. Other types of motor nerve growth, such as nerve regeneration, were unaffected by these agents. Our results are consistent with the concept that extrajunctional AChRs in skeletal muscle play an important role in the control of motor nerve terminal outgrowth at neuromuscular junctions.