The Role of Neuropeptide CGRP in the Regulation of Neurotransmitter Release in Regenerating Mouse Neuromuscular Junctions

We have previously found that in mature mouse motor synapses calcitonin gene-related peptide (CGRP) causes an increase in the size of acetylcholine (ACh) quanta and described a complex molecular cascade leading to the release of endogenous CGRP and a subsequent increase in the amplitude of miniature end plate potentials (MEPPs) after long-term synaptic activity (i.e., in the post-tetanic period). In functionally immature motor synapses regenerating after nerve injury, mechanisms that facilitate synaptic transmission are of particular interest as a potential way of influencing the processes of skeletal muscle reinnervation. In this work, we tested how exogenous CGRP affects spontaneous and evoked activity of regenerating motor synapses. Also, using the stimulation mode developed for modeling tetanic activity (2 min, 30 Hz), we described the presence of a post-tetanic increase in the amplitude of MEPPs caused by the release of endogenous CGRP in such synapses. As a result, we are the first to discover an acute, receptor-specific, potentiating effect of exogenous CGRP, as well as the possibility of endogenous CGRP exocytosis followed by subsequent activation of a molecular cascade involving the release of stored calcium and activation of protein kinases A and C, which leads to an increase in the size of ACh quanta in regenerating mouse motor synapses.