Mechanisms of postsynaptic plasticity: remodeling of the junctional acetylcholine receptor cluster induced by motor nerve terminal outgrowth.
Motor nerve terminal outgrowth (NTO) at neuromuscular junctions (NMJs) occurs rapidly in response to denervation changes in muscle. We have previously found that NTO can produce an elongation of the synaptic area of the NMJ as defined by cholinesterase-silver staining. In the present study, we examined the effects of NTO on a postsynaptic muscle membrane component, the usually stable cluster of acetylcholine receptors (AChRs) at the NMJ. NTO was evoked in rat soleus muscles using botulinum toxin. AChRs were demonstrated using immunocytochemistry or autoradiography of alpha-bungarotoxin binding. Our results show that NTO induces rapid elongation of the cluster of AChRs at the NMJ within 7 d of treatment with botulinum toxin. The growth in the size of the AChR clusters was accompanied by an increase in the number of AChRs/NMJ. No elongation of AChR clusters was seen following surgical denervation, suggesting that cluster growth is related to NTO and not to denervation changes in muscle per se. Growth of NMJ-AChR clusters appeared to result primarily from 2 processes: insertion of new AChRs into the NMJ membrane and, surprisingly, redistribution of preexisting NMJ-AChRs. These results show that NTO can cause rapid changes in the normally stable cluster of AChRs at the NMJ. Motor nerve terminals provide a strong and anatomically precise control of AChRs at the NMJ.
Yee
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WC
Pestronk
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D000818:Animals; D001345:Autoradiography; D001905:Botulinum Toxins / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002802:Cholinesterases / Q000032:analysis; D005260:Female; D006651:Histocytochemistry; D007124:Immunoenzyme Techniques; D009046:Motor Neurons / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D009473:Neuronal Plasticity; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism*
D002038:Bungarotoxins; D011950:Receptors, Cholinergic; D002802:Cholinesterases; D001905:Botulinum Toxins