Titre :
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Neuromuscular transmission and synaptic remodeling at the neuromuscular junction of knockout mice with partial deletions in the acetylcholinesterase gene (abstract : congrès international de Myologie, 2005)
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contenu dans :
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Auteurs :
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Congrès international de myologie 2005 (International Congress of Myology 2005; 9-13 mai 2005; Nantes, France) ;
Girard E ;
Camp S ;
Taylor P ;
Krejci E ;
Molgo J
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Type de document :
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Article
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Année de publication :
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2005
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Pages :
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p. 150
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Langues:
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Anglais
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Mots-clés :
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acétylcholinestérase
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activité enzymatique
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butyrylcholinestérase
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collagène Q
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colloque
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gène ACHE
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jonction neuromusculaire
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microscopie laser
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muscle squelettique
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mutation génétique
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récepteur nicotinique
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régulation métabolique
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souris
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Résumé :
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Communication n° 559 At the neuromuscular junction (NMJ) two closely related enzymes can hydrolyze acetylcholine (ACh): acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Although the role of AChE in regulating the duration of ACh action is well established, the role of BChE remains controversial. Advances in mouse genomics offered new approaches to assess the function of cholinesterases involved in synaptic transmission. For this purpose, we used mice with an altered localisation of AChE. At the NMJ, AChE is clustered by the interaction of the coding sequence of exon 6 with a specific collagen ColQ. The deletion of exons 5 and 6 in AChE gene transforms anchored AChE into a soluble enzyme, whereas the replacement of the exon 5 by the selection cassette Neo (deleted exon 5/Neo) reduced the expression of AChE to a very low level. The present study was designed to evaluate neuromuscular transmission and the eventual role BChE in these mice with partial deficit in AChE. The kinetics of the current flowing through the endplate membrane in response to an ACh quantum, as well as nerve-evoked muscle twitch and tetanic tensions were analyzed in isolated phrenic-hemidiaphragm neuromuscular preparations from the two transgenic mice. Additional information was obtained by confocal laser scanning microscopy of the endplate region of the transgenic muscles in order to determine the characteristics of muscle nicotinic ACh receptor clustering. The results obtained indicate that focally recorded miniature endplate currents (MEPC) exhibit a prolonged decay time in the transgenic junctions examined. Complementary morphological examination revealed that there is an important pre- and post-synaptic remodeling with a different distribution of motor nerve endings and clustering of muscle nicotinic ACh receptors at junctions from AChE deleted exons 5+6 muscles. These results will be discussed in terms of physiological adaptation or compensation for the absence of AChE activity.
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