Regulation of acetylcholinesterase appearance at neuromuscular junctions in vitro

Rubin, Lee L.; Schuetze, Stephen M.; Weill, Cheryl L.; Fischbach, Gerald D.

doi:10.1038/283264a0

Cited by 152 publications

(93 citation statements)

References 28 publications

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“…It has been suggested that, while clustering of AChRs at the nervemuscle contact does not depend on muscle activity, the loss of multi-endplate status and accumulation of AChE may depend on muscle activity (Giacobini et al, 1973;Lomo and Slater, 1978;Rubin et al, 1980;and review in Bennett, 1983). Development of organized neuromuscular junctions in the rat has also been considered to be linked to muscle activity (Lomo et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

Human muscle cultured in monolayer and cocultured with fetal rat spinal cord: importance of dorsal root ganglia for achieving successful functional innervation

1987

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Adult human muscle cultured in monolayer was cocultured with explants of 13-14-d-old rat embryo using (a) ventral spinal cord (VSC), (b) transverse section of whole spinal cord (WSC), and (c) WSC with dorsal root ganglia (DRG) attached (WSC + DRG). AChR clusters and AChE- positive patches, both at the nerve-muscle contacts, were studied at 5, 12, and 21 d of coculture with each of the 3 spinal cord preparations. In addition, AChE-positive patches were studied after 31-64 d of coculture with WSC + DRG to evaluate further organization of those patches. Compared to VSC and WSC cocultures, WSC + DRG induced significantly more AChR clusters per muscle fiber at the nerve-muscle contacts at 5 d of coculture, and the percentage of muscle fibers containing AChR clusters was higher at all 3 time points quantitated. The number of AChE-positive sites was the same with all 3 spinal cord preparations in early (day 5) cocultures. Between 12 and 21 d of coculture, the number of muscle fibers containing AChE patches increased significantly only with WSC + DRG, correlating with the increased number of contracting muscle fibers in that coculture system. Only in human muscle cocultured with WSC + DRG was successful innervation of the cultured muscle fibers achieved, as manifested by (1) contractions in a continuous rhythm of large groups of muscle fibers that were reversibly blocked by 1 mM d-tubocurarine (aneurally cultured human muscle does not spontaneously contract); (2) well- developed cross-striations throughout the fiber; (3) well-organized AChE-positive sites; and (4) a trend from multifocal toward unifocal innervation of those muscle fibers. Our studies demonstrate that adult human muscle cultured in monolayer can be innervated by fetal rat spinal cord and that, in our system, DRG are essential for achieving functional innervation.

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Section: Discussionmentioning

confidence: 99%

Human muscle cultured in monolayer and cocultured with fetal rat spinal cord: importance of dorsal root ganglia for achieving successful functional innervation

1987

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“…La stimulation du muscle squelettique adulte provoque une augmentation très importante de la concentration en GMPc musculaire (Nestler et al, 1978). De même, l'addition de GMPc à des cultures de muscle mime les effets de l'activité sur l'AChE synaptique (Rubin et al, 1980 Fambrough, 1983 ;Sanes et Chiu, 1983 (1983,1984), Nitkin etal. (1983Nitkin etal.…”

Section: A) Propriétés Des Fibres Musculairesunclassified

Propriétés des fibres musculaires squelettiques. 1. Influence de l'innervation motrice

Bacou¹,

Vigneron²

1988

Reprod. Nutr. Dévelop.

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“…Incompetent neurons, such as those of dorsal root ganglia and other noncholinergic neurons, are ineffective in this regard, thereby emphasizing the neural specificity of the triggering interaction (Cohen and Weldon, 1980;Role et al, 1985). The neural agent(s) that initiates these remarkable changes in AChR distribution has not yet been identified, but it is known that it can act in the absence of activation of AChRs, as well as in the absence of muscle and neuronal action potentials Rubin et al, 1980;Davey and Cohen, 1986). The response of the muscle cell to the triggering event includes a process of receptor redistribution whereby preexisting mobile AChRs in neighboring regions of the surface membrane aggregate along the path of neurite-muscle contact where they become immobilized Stya and Axelrod, 1984;Ziskind-Conhaim et al, 1984;Kidokoro et al, 1986).…”

mentioning

confidence: 99%

Distribution of synaptic specializations along isolated motor units formed in Xenopus nerve-muscle cultures

Cohen¹,

Rodriguez-Marin²,

Wilson³

1987

J. Neurosci.

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The capacity of individual muscle cells and neurons to establish synaptic specializations along the entire extent of their neurite- muscle contacts was assessed in culture. Spinal cord neurons derived from embryos of Xenopus laevis were plated at low density in cultures of Xenopus myotomal muscle cells in order to obtain isolated motor units whose neuron and muscle cells were not contacted by any other neuron. These isolated motor units were examined for localization of acetylcholine receptors (AChRs) after staining with fluorescent alpha- bungarotoxin and, in some cases, for localization of a synaptic vesicle antigen by immunofluorescence. The neurite-muscle contacts formed by competent neurons exhibited discontinuous sites of AChR localization occupying about 25% of the contact length as compared with 2% for incompetent neurons. Competent neurons, unlike incompetent ones, established these neurite-associated receptor patches (NARPs) on virtually all the muscle cells they contacted and functionally innervated them. These and other observations on the distribution of NARPs throughout the isolated motor units indicate that the capacity of competent neurons to establish NARPs extends to the limits of growth of most if not all of their neurites, that this capacity is least in the most proximal portions of initial neuritic segments, and that the overall capacity of muscle cells to generate NARPs can be saturated by long lengths of neurite-muscle contact. The results also suggest that even in the absence of competitive interactions between neurons there are spatial discontinuities in neuritic action and/or muscle response during the establishment of NARPs. Synaptic vesicle antigen patches (SVAPs) occurred along the neuritic arbor of all neurons, but their distribution in competent neurons (those which established NARPs) and in incompetent ones differed. For competent neurons the percentage of neurite length occupied by SVAPs was 4.8-fold greater on muscle cells than off, whereas the corresponding value for incompetent neurons was only 1.5-fold. This large preferential localization of SVAPs along neurite-muscle contacts of competent neurons was further associated with a colocalization of SVAPs and NARPs that was greater than predicted by chance. These results suggest that muscle cells are much more effective in influencing the distribution of synaptic vesicles along the neuritic arbor of competent neurons than along the arbor of incompetent neurons and that this influence is greatest at sites of postsynaptic differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)

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Regulation of acetylcholinesterase appearance at neuromuscular junctions in vitro

Cited by 152 publications

References 28 publications

Human muscle cultured in monolayer and cocultured with fetal rat spinal cord: importance of dorsal root ganglia for achieving successful functional innervation

Human muscle cultured in monolayer and cocultured with fetal rat spinal cord: importance of dorsal root ganglia for achieving successful functional innervation

Propriétés des fibres musculaires squelettiques. 1. Influence de l'innervation motrice

Distribution of synaptic specializations along isolated motor units formed in Xenopus nerve-muscle cultures

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