title: Calcitonin gene-related peptide potentiates synaptic responses at developing neuromuscular junction.
abstract: Protein phosphorylation is important in synaptic transmission and plasticity. At the neuromuscular junction, phosphorylation of acetylcholine (ACh) receptor-channels increases the rate of agonist-induced channel desensitization. In contrast, potentiation of ACh channel activity through protein phosphorylation has not been described. We report here that calcitonin gene-related peptide (CGRP), a neuropeptide present at presynaptic motor nerve terminals, enhances the postsynaptic response at developing neuromuscular junctions by increasing the burst duration of embryonic ACh channels. The effect of CGRP on these ACh channels is mimicked by dibutyryl-cyclic AMP and by cAMP-dependent protein kinase (PKA) and prevented by a specific peptide inhibitor of PKA. Moreover, postsynaptic inhibition of PKA reduced the amplitude and decay time of spontaneous synaptic currents, suggesting that endogenous CGRP may act as a potentiating factor during the early phase of synaptogenesis.
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York 10021.
authors.forename: B
authors.initials: B
authors.lastname: Lu
authors.forename: W M
authors.initials: WM
authors.lastname: Fu
authors.forename: P
authors.initials: P
authors.lastname: Greengard
authors.forename: M M
authors.initials: MM
authors.lastname: Poo
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D046508:Culture Techniques; D007473:Ion Channels / Q000378:metabolism; D008564:Membrane Potentials; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009469:Neuromuscular Junction / Q000196:embryology / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D014981:Xenopus
chemical_list: D007473:Ion Channels; D011494:Protein Kinases; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine