Protease inhibitors reduce the loss of nerve terminals induced by activity and calcium in developing rat soleus muscles in vitro - PubMed (original) (raw)
Protease inhibitors reduce the loss of nerve terminals induced by activity and calcium in developing rat soleus muscles in vitro
R A O'Brien et al. Neuroscience. 1984 Jun.
Abstract
The end-plate of a mammalian skeletal muscle fibre is innervated by several axons at the time of birth but by only one axon in the adult. In the rat soleus muscle the transition from polyneuronal to single innervation occurs during the first 2-3 weeks after birth. While it is evident that the loss of the excess nerve terminals depends to some extent on neuromuscular activity, the mechanism involved is not known. In the present experiments neonatal rat soleus muscles were stimulated in vitro in the presence of a variety of combinations of calcium, the cholinesterase inhibitor edrophonium and the proteolytic enzyme inhibitors leupeptin, pepstatin and Ep-475. Electron microscopical examination revealed that stimulation alone had little effect on the morphology of the end-plate region but stimulation in the presence of raised levels of calcium caused severe disruption of the nerve terminals and a marked reduction in the number of intact nerve terminal profiles contacting each end-plate. Contraction measurements showed that, in spite of this, the muscles were not functionally denervated to any large extent. The addition of edrophonium potentiated the morphological alterations but caused no further reduction in the number of profiles. Conversely, the protease inhibitors wholly or partially (in the case of Ep-475) prevented the effects of stimulation and calcium on the nerve terminals. These results are consistent with the idea that neuromuscular activity induces the secretion of proteolytic enzymes into the end-plate region, where they digest the immature nerve terminals. The importance of calcium suggests that the calcium-dependent neutral protease may be involved, and is also consistent with a secretory mechanism. The possibility that the nerve terminals are digested by their own proteases is also discussed.
Similar articles
- Observations on the elimination of polyneuronal innervation in developing mammalian skeletal muscle.
O'Brien RA, Ostberg AJ, Vrbová G. O'Brien RA, et al. J Physiol. 1978 Sep;282:571-82. doi: 10.1113/jphysiol.1978.sp012482. J Physiol. 1978. PMID: 722562 Free PMC article. - Polyneuronal innervation of skeletal muscle in new-born rats and its elimination during maturation.
Brown MC, Jansen JK, Van Essen D. Brown MC, et al. J Physiol. 1976 Oct;261(2):387-422. doi: 10.1113/jphysiol.1976.sp011565. J Physiol. 1976. PMID: 978579 Free PMC article. - Selective elimination of motor nerve terminals in the rat soleus muscle during development.
Miyata Y, Yoshioka K. Miyata Y, et al. J Physiol. 1980 Dec;309:631-46. doi: 10.1113/jphysiol.1980.sp013531. J Physiol. 1980. PMID: 6942157 Free PMC article. - Effect of low calcium and protease inhibitors on synapse elimination during postnatal development in the rat soleus muscle.
Connold AL, Evers JV, Vrbová G. Connold AL, et al. Brain Res. 1986 Jul;393(1):99-107. doi: 10.1016/0165-3806(86)90069-6. Brain Res. 1986. PMID: 3015360 - Reorganization of synaptic inputs to developing skeletal muscle fibres.
Vrbová G, Lowrie MB, Evers J. Vrbová G, et al. Ciba Found Symp. 1988;138:131-51. doi: 10.1002/9780470513675.ch9. Ciba Found Symp. 1988. PMID: 3197514
Cited by
- Blocking skeletal muscle DHPRs/Ryr1 prevents neuromuscular synapse loss in mutant mice deficient in type III Neuregulin 1 (CRD-Nrg1).
Liu Y, Sugiura Y, Chen F, Lee KF, Ye Q, Lin W. Liu Y, et al. PLoS Genet. 2019 Mar 14;15(3):e1007857. doi: 10.1371/journal.pgen.1007857. eCollection 2019 Mar. PLoS Genet. 2019. PMID: 30870432 Free PMC article. - Calcium dependence of damage to mouse motor nerve terminals following oxygen/glucose deprivation.
Talbot JD, David G, Barrett EF, Barrett JN. Talbot JD, et al. Exp Neurol. 2012 Mar;234(1):95-104. doi: 10.1016/j.expneurol.2011.12.020. Epub 2011 Dec 27. Exp Neurol. 2012. PMID: 22206924 Free PMC article. - Calpain activation impairs neuromuscular transmission in a mouse model of the slow-channel myasthenic syndrome.
Groshong JS, Spencer MJ, Bhattacharyya BJ, Kudryashova E, Vohra BP, Zayas R, Wollmann RL, Miller RJ, Gomez CM. Groshong JS, et al. J Clin Invest. 2007 Oct;117(10):2903-12. doi: 10.1172/JCI30383. J Clin Invest. 2007. PMID: 17853947 Free PMC article. - Tissue inhibitor of metalloproteinase-2(TIMP-2)-deficient mice display motor deficits.
Jaworski DM, Soloway P, Caterina J, Falls WA. Jaworski DM, et al. J Neurobiol. 2006 Jan;66(1):82-94. doi: 10.1002/neu.20205. J Neurobiol. 2006. PMID: 16216006 Free PMC article. - Intercellular communication that mediates formation of the neuromuscular junction.
Daniels MP. Daniels MP. Mol Neurobiol. 1997 Jun;14(3):143-70. doi: 10.1007/BF02740654. Mol Neurobiol. 1997. PMID: 9294861 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources