Regulation of postsynaptic responses by calcitonin gene related peptide and ATP at developing neuromuscular junctions.
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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Roche Institute of Molecular Biology, Nutley, NJ 07110, USA.
Fu
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WM
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006801:Humans; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011950:Receptors, Cholinergic / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D014981:Xenopus
D011950:Receptors, Cholinergic; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D015740:Calcitonin Gene-Related Peptide