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Delayed increase of acetylcholine quantal size induced by the activity‐dependent release of endogenous CGRP but not ATP in neuromuscular junctions
Author(s) -
Bogacheva Polina,
Balezina Olga
Publication year - 2020
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.22175
Subject(s) - long term potentiation , chemistry , calcitonin gene related peptide , neuromuscular junction , acetylcholine , ryanodine receptor , tetanic stimulation , acetylcholine receptor , synaptic vesicle , neuroscience , stimulation , biophysics , synaptic cleft , endocrinology , neurotransmission , receptor , neuropeptide , vesicle , biochemistry , biology , membrane
In mouse motor synapses tetanic neuromuscular activity (30 Hz, 2 min) led to a delayed posttetanic potentiation of amplitude and duration of spontaneous miniature endplate potentials (MEPPs). Microelectrode recordings of MEPPs before and after nerve stimulation showed an increase in MEPP amplitude and time course by 30% and 15%, respectively, without changes in their frequency. Peak effect was detected 20 min after tetanic activity and progressively faded throughout the next 40 min of recording. The revealed potentiation of MEPPs was fully preserved in preparations from pannexin 1 knockout mice. It means, that myogenic ATP released via pannexin 1 channels from contracting muscle fibers is not likely to participate in the described phenomenon. But posttetanic potentiation of MEPPs was fully prevented by competitive antagonist of calcitonin gene‐related peptide (CGRP) receptors CGRP 8‐37 , ryanodine receptors inhibitor ryanodine and by vesicular acetylcholine transporter inhibitor vesamicol. It is suggested that the combination of intensive synaptic and contractile activity in neuromuscular junctions is required to induce Ca 2+ ‐dependent exocytosis of endogenous CGRP. The accumulation of CGRP in the synaptic cleft and its presynaptic activity may induce posttetanic potentiation of MEPP amplitude due to CGRP‐stimulated acetylcholine loading into vesicles and subsequent increase of quantal size.