EXPERIMENTAL ACETYLCHOLINE BLOCKADE OF THE NEUROMUSCULAR JUNCTION. EFFECTS ON END PLATE AND MUSCLE FIBER ULTRASTRUCTURE*

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Abstract
To investigate the effect of acetylcholine on the formation and maintenance of the end plate, presynaptic (hemicholinium-3 and botulinum toxin) and postsynaptic (curare and alpha-bungarotoxin) blocking agents were injected into the amniotic sac or chorioallantoic circulation of chick embryos during different stages of their development (days 3 to 11, 3 to 18, and 12 to 18). Tntercostal or anterior and posterior latissimus dorsi muscles were examined by electron microscopy. Regardless of the duration of treatment, the type of agent, or the type of muscle, nerve ingrowth into muscle and end-plate formation were not arrested and the ultrastructure of nerve terminals and postsynaptic regions was normal. By contrast, muscle fiber ultrastructure was affected by acetylcholine blockade if continued beyond day 11. By day 11 both treated and control muscles were composed primarily of myotubes. Muscles treated beyond day 11 showed impaired fiber differentiation and persistence of many myotubes. In addition, many fiber regions contained unassembled fine filaments intermingled with other organelles. In hemicholinium-3 treated muscles ther were also mitochondrial abnormalities and an increased number of lipid droplets. The findings suggest that the altered structure of the neuromusclar junction in myasthenia gravis is not due to the lack of a trophic effect of acetylcholine. The impaired fiber maturation in the chick embryos may be related to the lack of acetylcholine mediated fiber activity.

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