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Volume 17, Number 7,
Issue of April 1, 1997
pp. 2459-2468
Copyright ©1997 Society for Neuroscience
Regulation of Quantal Secretion from Developing Motoneurons by
Postsynaptic Activity-Dependent Release of NT-3
Received Sept. 17, 1996; revised Jan. 14, 1997; accepted Jan. 22, 1997.
Jau-Cheng Liou and
Wen-Mei Fu
Pharmacological Institute, College of Medicine, National Taiwan
University, Taipei, Taiwan 100
Neurotrophic factors derived from postsynaptic muscle cells may
play important roles in the development of presynaptic neuronal functions. In 3-d-old Xenopus nerve-muscle cultures,
embryonic spinal neurons that had made natural contact with co-cultured myocytes exhibited spontaneous release of larger packets of
acetylcholine (ACh) quanta than those released by the isolated neurons
having no contact with any myocyte. Treatment of isolated neurons with neurotrophin-3 (NT-3) for 2 d increased the average sizes of
quantal ACh packets at newly formed nerve-muscle synapses, whereas
treatment with antibody against NT-3 or with K252a, a specific
inhibitor of tyrosine kinase receptors, decreased the quantal size at
existing synapses, which suggests that NT-3 supplied by the
postsynaptic muscle cell may be responsible for the development and
maintenance of the quantal packets. The muscle effect seems to depend
on synaptic activities mediated by postsynaptic ACh receptor channels,
because chronic treatment of the culture with
D-tubocurarine (D-Tc) for 2 d resulted in
a marked reduction of the quantal sizes, when assayed after extensive
washing of the culture with Ringer's solution. The curare treatment
did not affect the postsynaptic ACh receptor sensitivity, because
iontophoretically applied ACh induced current responses similar to
those of control. Finally, co-treatment of the culture with NT-3 and
D-Tc reversed the effect of D-Tc on the quantal
size, and this reversal effect was abolished when K252a was also
applied concomitantly. Our results suggest that muscle-derived NT-3
participates in the maturation of normal transmitter packets in
developing neurons, and the secretion of NT-3 depends on spontaneous
synaptic activity.
Key words:
neurotrophin-3;
neurotrophic factor;
neuromuscular
junction;
synaptogenesis;
Xenopus laevis;
neuronal
activity
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