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. 1990 Aug 1;111(2):655–661. doi: 10.1083/jcb.111.2.655

Metabolic stabilization of acetylcholine receptors in vertebrate neuromuscular junction by muscle activity

PMCID: PMC2116192  PMID: 2380246

Abstract

The effects of muscle activity on the growth of synaptic acetylcholine receptor (AChR) accumulations and on the metabolic AChR stability were investigated in rat skeletal muscle. Ectopic end plates induced surgically in adult soleus muscle were denervated early during development when junctional AChR number and stability were still low and, subsequently, muscles were either left inactive or they were kept active by chronic exogenous stimulation. AChR numbers per ectopic AChR cluster and AChR stabilities were estimated from the radioactivity and its decay with time, respectively, of end plate sites whose AChRs had been labeled with 125I-alpha-bungarotoxin (alpha-butx). The results show that the metabolic stability of the AChRs in ectopic clusters is reversibly increased by muscle activity even when innervation is eliminated very early in development. 1 d of stimulation is sufficient to stabilize the AChRs in ectopic AChR clusters. Muscle stimulation also produced an increase in the number of AChRs at early denervated end plates. Activity-induced cluster growth occurs mainly by an increase in area rather than in AChR density, and for at least 10 d after denervation is comparable to that in normally developing ectopic end plates. The possible involvement of AChR stabilization in end plate growth is discussed.

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Selected References

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  1. Avila O. L., Drachman D. B., Pestronk A. Neurotransmission regulates stability of acetylcholine receptors at the neuromuscular junction. J Neurosci. 1989 Aug;9(8):2902–2906. doi: 10.1523/JNEUROSCI.09-08-02902.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bevan S., Steinbach J. H. Denervation increases the degradation rate of acetylcholine receptors at end-plates in vivo and in vitro. J Physiol. 1983 Mar;336:159–177. doi: 10.1113/jphysiol.1983.sp014574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brenner H. R., Rudin W. On the effect of muscle activity on the end-plate membrane in denervated mouse muscle. J Physiol. 1989 Mar;410:501–512. doi: 10.1113/jphysiol.1989.sp017546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brett R. S., Younkin S. G., Konieczkowski M., Slugg R. M. Accelerated degradation of junctional acetylcholine receptor-alpha-bungarotoxin complexes in denervated rat diaphragm. Brain Res. 1982 Feb 4;233(1):133–142. doi: 10.1016/0006-8993(82)90935-0. [DOI] [PubMed] [Google Scholar]
  5. Burden S. Acetylcholine receptors at the neuromuscular junction: developmental change in receptor turnover. Dev Biol. 1977 Nov;61(1):79–85. doi: 10.1016/0012-1606(77)90343-8. [DOI] [PubMed] [Google Scholar]
  6. Fallon J. R., Nitkin R. M., Reist N. E., Wallace B. G., McMahan U. J. Acetylcholine receptor-aggregating factor is similar to molecules concentrated at neuromuscular junctions. Nature. 1985 Jun 13;315(6020):571–574. doi: 10.1038/315571a0. [DOI] [PubMed] [Google Scholar]
  7. Fontaine B., Changeux J. P. Localization of nicotinic acetylcholine receptor alpha-subunit transcripts during myogenesis and motor endplate development in the chick. J Cell Biol. 1989 Mar;108(3):1025–1037. doi: 10.1083/jcb.108.3.1025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frank E., Jansen J. K., Lomo T., Westgaard R. H. The interaction between foreign and original motor nerves innervating the soleus muscle of rats. J Physiol. 1975 Jun;247(3):725–743. doi: 10.1113/jphysiol.1975.sp010954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. KARNOVSKY M. J. THE LOCALIZATION OF CHOLINESTERASE ACTIVITY IN RAT CARDIAC MUSCLE BY ELECTRON MICROSCOPY. J Cell Biol. 1964 Nov;23:217–232. doi: 10.1083/jcb.23.2.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Levitt T. A., Loring R. H., Salpeter M. M. Neuronal control of acetylcholine receptor turnover rate at a vertebrate neuromuscular junction. Science. 1980 Oct 31;210(4469):550–551. doi: 10.1126/science.7423205. [DOI] [PubMed] [Google Scholar]
  11. Loring R. H., Salpeter M. M. Denervation increases turnover rate of junctional acetylcholine receptors. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2293–2297. doi: 10.1073/pnas.77.4.2293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lømo T., Massoulié J., Vigny M. Stimulation of denervated rat soleus muscle with fast and slow activity patterns induces different expression of acetylcholinesterase molecular forms. J Neurosci. 1985 May;5(5):1180–1187. doi: 10.1523/JNEUROSCI.05-05-01180.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lømo T., Pockett S., Sommerschild H. Control of number and distribution of synapses during ectopic synapse formation in adult rat soleus muscles. Neuroscience. 1988 Feb;24(2):673–686. doi: 10.1016/0306-4522(88)90360-0. [DOI] [PubMed] [Google Scholar]
  14. Lømo T., Slater C. R. Acetylcholine sensitivity of developing ectopic nerve-muscle junctions in adult rat soleus muscles. J Physiol. 1980 Jun;303:173–189. doi: 10.1113/jphysiol.1980.sp013279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Magill-Solc C., McMahan U. J. Motor neurons contain agrin-like molecules. J Cell Biol. 1988 Nov;107(5):1825–1833. doi: 10.1083/jcb.107.5.1825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Michler A., Sakmann B. Receptor stability and channel conversion in the subsynaptic membrane of the developing mammalian neuromuscular junction. Dev Biol. 1980 Nov;80(1):1–17. doi: 10.1016/0012-1606(80)90494-7. [DOI] [PubMed] [Google Scholar]
  17. Nitkin R. M., Smith M. A., Magill C., Fallon J. R., Yao Y. M., Wallace B. G., McMahan U. J. Identification of agrin, a synaptic organizing protein from Torpedo electric organ. J Cell Biol. 1987 Dec;105(6 Pt 1):2471–2478. doi: 10.1083/jcb.105.6.2471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pestronk A. Intracellular acetylcholine receptors in skeletal muscles of the adult rat. J Neurosci. 1985 May;5(5):1111–1117. doi: 10.1523/JNEUROSCI.05-05-01111.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Podleski T. R., Salpeter M. M. Acetylcholine receptor clustering and triton solubility: neural effect. J Neurobiol. 1988 Mar;19(2):167–185. doi: 10.1002/neu.480190206. [DOI] [PubMed] [Google Scholar]
  20. Salpeter M. M., Cooper D. L., Levitt-Gilmour T. Degradation rates of acetylcholine receptors can be modified in the postjunctional plasma membrane of the vertebrate neuromuscular junction. J Cell Biol. 1986 Oct;103(4):1399–1403. doi: 10.1083/jcb.103.4.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Salpeter M. M., Loring R. H. Nicotinic acetylcholine receptors in vertebrate muscle: properties, distribution and neural control. Prog Neurobiol. 1985;25(4):297–325. doi: 10.1016/0301-0082(85)90018-8. [DOI] [PubMed] [Google Scholar]
  22. Schuetze S. M., Role L. W. Developmental regulation of nicotinic acetylcholine receptors. Annu Rev Neurosci. 1987;10:403–457. doi: 10.1146/annurev.ne.10.030187.002155. [DOI] [PubMed] [Google Scholar]
  23. Shyng S. L., Salpeter M. M. Degradation rate of acetylcholine receptors inserted into denervated vertebrate neuromuscular junctions. J Cell Biol. 1989 Feb;108(2):647–651. doi: 10.1083/jcb.108.2.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Slater C. R. Neural influence on the postnatal changes in acetylcholine receptor distribution at nerve-muscle junctions in the mouse. Dev Biol. 1982 Nov;94(1):23–30. doi: 10.1016/0012-1606(82)90064-1. [DOI] [PubMed] [Google Scholar]
  25. Stanley E. F., Drachman D. B. Denervation accelerates the degradation of junctional acetylcholine receptors. Exp Neurol. 1981 Aug;73(2):390–396. doi: 10.1016/0014-4886(81)90274-0. [DOI] [PubMed] [Google Scholar]
  26. Wallace B. G. Aggregating factor from Torpedo electric organ induces patches containing acetylcholine receptors, acetylcholinesterase, and butyrylcholinesterase on cultured myotubes. J Cell Biol. 1986 Mar;102(3):783–794. doi: 10.1083/jcb.102.3.783. [DOI] [PMC free article] [PubMed] [Google Scholar]

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