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Noncanonical Potentiation of Evoked Quantal Release of Acetylcholine by Cannabinoids Anandamide and 2-Arachidonoylglycerol in Mouse Motor Synapses

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

Abstract

We studied the effects of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) on the evoked activity of neuromuscular junctions (NMJs) of mouse diaphragm and m. extensor digitorum longus (m. EDL). Using the microelectrode technique, spontaneous miniature endplate potentials (MEPPs) and multiquantal endplate potentials (EPPs) evoked by short rhythmic nerve stimulation trains (50 Hz, 1 s) were recorded. AEA (30 µM) caused an increase in the MEPP frequency but not in the MEPP amplitude, which lead to an increase in amplitude and quantal content (QC) of each EPP in a train. Quantal analysis showed that AEA causes an enlargement of the size of the readily releasable pool (RRP) of vesicles in motor terminals. The AEA-induced increase in EPP amplitude and QC was prevented by L-type Ca2+-channel blocker nitrendipine (1 µM), which suggests that this channel type is upregulated upon the AEA application. 2-AG (1 µM) caused an increase in MEPP amplitude but not in their frequency in mouse diaphragm NMJs. This was accompanied by an increase in the EPP amplitude, whereas their QC remained at the control level. The same effect was reproduced in synapses of m. EDL. The rise of the EPP amplitude caused by 2-AG was prevented by PKA inhibition by H-89 (1 µM). These data, together with previous evidence that blocking vesicular transport of acetylcholine (ACh) abolishes the 2-AG-induced increase in MEPP amplitude, allows us to suggest that 2-AG stimulates ACh pumping into vesicles in a PKA-dependent way, thus causing an increase in the size of a single ACh quanta. This work is the first to show a fast noncanonical facilitating action of AEA and 2-AG on the evoked activity of mouse NMJ. AEA and 2-AG cause similar presynaptic and CB1-receptor-dependent changes of neuromuscular transmission, but they exert their effects through two different ways, leading to facilitation of different parameters of ACh secretion.

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ACKNOWLEDGMENTS

The work was supported by the Russian Foundation for Basic Research (project no. 19-04-00616-a).

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Authors and Affiliations

  1. Biology Department, Moscow Lomonosov State University, 119234, Moscow, Russia

    E. O. Tarasova, N. A. Khotkina, P. O. Bogacheva, K. A. Chernyshev, A. E. Gaydukov & O. P. Balezina

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  1. E. O. Tarasova
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  2. N. A. Khotkina
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Correspondence to A. E. Gaydukov.

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All experimental procedures were performed in accordance with Directive 86/609/EEC on the treatment of humans and laboratory animals and were approved by the Bioethics Commission of the Faculty of Biology of the Moscow State University.

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Translated by A. Dunina-Barkovskaya

Abbreviations: AEA, anadamide; 2-AG, 2-arachidonoylglycerol; CNS, central nervous system; EPPs, endplate potentials; m. EDL, musculus extensor digitorum longus; MEPPs, miniature endplate potentials; NMJs, neuromuscular junctions; RRP, readily releasable pool.

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Tarasova, E.O., Khotkina, N.A., Bogacheva, P.O. et al. Noncanonical Potentiation of Evoked Quantal Release of Acetylcholine by Cannabinoids Anandamide and 2-Arachidonoylglycerol in Mouse Motor Synapses. Biochem. Moscow Suppl. Ser. A 15, 395–405 (2021). https://doi.org/10.1134/S199074782106012X

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