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Can J Physiol Pharmacol. 1995 Jul;73(7):1050-6.

Regulation of postsynaptic responses by calcitonin gene related peptide and ATP at developing neuromuscular junctions.

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Roche Institute of Molecular Biology, Nutley, NJ 07110, USA.


Neuronal factors co-released with neurotransmitters may play an important role in synapse development and function. Calcitonin gene related peptide (CGRP) and adenosine 5'-triphosphate (ATP), two principal neuromodulators present in the motor nerve terminals, were studied for their roles and mechanisms during early development of neuromuscular synapses in Xenopus nerve--muscle co-cultures. CGRP treatment increased the decay time and amplitude of spontaneous synaptic currents (SSCs) recorded from innervated myocytes, without affecting SSC frequency, suggesting a postsynaptic mechanism. ATP also increased the SSC amplitude and decay time. In addition, ATP was shown to potentiate the responses of isolated myocytes to iontophoretically applied acetylcholine (ACh). Single-channel recording from isolate myocytes showed that both CGRP and ATP specifically increased the open time of embryonic-type, low-conductance ACh channels. Pharmacological experiments suggest that the CGRP actions were mediated by cAMP-dependent protein kinase (PKA), while ATP exerted its effects by binding to P2 purinoceptors and thereby activating protein kinase C (PKC). Moreover, the effects of CGRP and ATP on ACh channel activity were restricted to immature myocytes. Taken together, these results suggest that endogenous CGRP and ATP co-released with ACh from the nerve terminal may promote synaptic development by potentiating postsynaptic ACh channel activity during the early phase of synaptogenesis.

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