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The Role of Endogenous Calcitonin Gene-Related Peptide in the Neurotransmitter Quantal Size Increase in Mouse Neuromuscular Junctions

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Changes in parameters of spontaneous acetylcholine (ACh) quantal secretion caused by prolonged high-frequency burst activity of neuromuscular junctions and possible involvement of endogenous calcitonin gene-related peptide (CGRP) and its receptors in these changes were studied. With this purpose, miniature endplate potentials (MEPPs) were recorded using standard microelectrode technique in isolated neuromuscular preparations of m. EDL–n. peroneus after a prolonged high-frequency nerve stimulation (30 Hz for 2 min). An increase in the MEPP amplitudes and time course was observed in the postactivation period that reached maximum 20–30 min after nerve stimulation and progressively faded in the following 30 min of recording. Inhibition of vesicular ACh transporter with vesamicol (1 μM) fully prevented this “wave” of the MEPP enhancement. This indicates the presynaptic origin of the MEPP amplitude increase, possibly mediated via intensification of synaptic vesicle loading with ACh and subsequent increase of the quantal size. Competitive antagonist of the CGRP receptor, truncated peptide isoform CGRP8–37 (1 μM), had no effect on spontaneous secretion parameters by itself but was able to prevent the appearance of enhanced MEPPs in the postactivation period. This suggests the involvement of endogenous CGRP and its receptors in the observed MEPP enhancement after an intensive nerve stimulation. Ryanodine in high concentration (1 μM) that blocks ryanodine receptors and stored calcium release did not influence spontaneous ACh secretion but prevented the increase of the MEPP parameters in the postactivation period. Altogether, the data indicate that an intensive nerve stimulation, which activates neuromuscular junctions and muscle contractions, leads to a release of endogenous CGRP into synaptic cleft and this release strongly depends on the efflux of stored calcium. The released endogenous CGRP is able to exert an acute presynaptic effect on nerve terminals, which involves its specific receptor action and intracellular cascades leading to intensification of ACh loading into synaptic vesicles and an increase in the ACh quantal size.

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Authors and Affiliations

  1. Faculty of Biology, Lomonosov Moscow State University, Moscow, 119234, Russia

    P. O. Bogacheva, E. A. Golikova & O. P. Balezina

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  1. P. O. Bogacheva
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  2. E. A. Golikova
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  3. O. P. Balezina
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Correspondence to P. O. Bogacheva.

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Original Russian Text © P.O. Bogacheva, E.A. Golikova, O.P. Balezina, 2018, published in Biologicheskie Membrany, 2018, Vol. 35, No. 4, pp. 297–308.

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Bogacheva, P.O., Golikova, E.A. & Balezina, O.P. The Role of Endogenous Calcitonin Gene-Related Peptide in the Neurotransmitter Quantal Size Increase in Mouse Neuromuscular Junctions. Biochem. Moscow Suppl. Ser. A 12, 268–277 (2018). https://doi.org/10.1134/S1990747818030029

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  • DOI: https://doi.org/10.1134/S1990747818030029

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