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Interaction between the Mechanisms of Suppression of Acetylcholine Quantal Secretion upon Activation of Vanilloid (TRPV1) and Purine Receptors in the Mouse Neuromuscular Synapse

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Abstract

The main goal of the study was to analyze the relationship between the signaling pathways regulating acetylcholine (ACh) quantal release in the peripheral synapse that are triggered by the activation of vanilloid (TRPV1) and purine receptors. In electrophysiological experiments carried out on the neuromuscular synapse of the mouse levator auris longus muscle, it was found that the frequency of miniature end-plate potentials (mEPPs) and the quantal content of end-plate potentials (EPPs) decrease in the presence of the TRPV1 receptor agonist capsaicin. This effect was completely reversed by SB 366791, a specific competitive TRPV1 receptor antagonist. ATP, like capsaicin, decreased the frequency of mEPPs and the EPP quantal content. In the presence of SB 366791, the inhibitory effect of ATP on ACh secretion realized its full. At the same time, in the presence of TRPV1 channel activation by capsaicin, the effect of ATP on both spontaneous and evoked ACh release was absent. It was suggested that the action mechanisms of ATP and capsaicin are underpinned by a change in Ca2+ entry into the nerve ending. To test this hypothesis, experiments were carried out to assess the changes in the presynaptic calcium level (Ca2+ transient) using a fluorescent calcium dye upon nerve stimulation. The amplitude of the Ca2+ transient did not change by either ATP application or capsaicin addition. Thus, in the neuromuscular synapse of mammals, along with the purinergic pathway of ACh secretion regulation, there is also a mechanism of neurosecretion modulation mediated by the activation of TRPV1 channels. The triggering of these mechanisms leads to the suppression of the processes of both spontaneous and evoked ACh quantal release from the motor nerve endings. It was demonstrated that both regulatory pathways are not accompanied by a change in the Ca2+ transient, but share a common link in ACh quantal release regulation.

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Funding

This study was supported by the Russian Foundation for Basic Research, grant no. 19-04-00490 (experimental part) and a budget funding within the Government assignment to Kazan Institute of Biochemistry and Biophysics, Kazan Scientific Center, Russian Academy of Sciences (processing of fluorescent images).

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Authors and Affiliations

  1. Kazan Institute of Biochemistry and Biophysics, Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russia

    A. Y. Arkhipov, N. V. Zhilyakov, A. I. Malomouzh & D. V. Samigullin

  2. A.N. Tupolev Kazan National Research Technical University, Kazan, Russia

    D. V. Samigullin

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  1. A. Y. Arkhipov
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  2. N. V. Zhilyakov
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  3. A. I. Malomouzh
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  4. D. V. Samigullin
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Contributions

Basic idea and planning of the experiments (A.Y.A. and D.V.S.); data collection (A.Y.A. and N.V.Z.); manuscript writing and editing (A.Y.A., A.I.M. and D.V.S.).

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Correspondence to D. V. Samigullin.

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The authors declare neither evident nor potential conflict of interest in relation to the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2021, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2021, Vol. 107, Nos. 4–5, pp. 647–660https://doi.org/10.31857/S0869813921040038.

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Arkhipov, A.Y., Zhilyakov, N.V., Malomouzh, A.I. et al. Interaction between the Mechanisms of Suppression of Acetylcholine Quantal Secretion upon Activation of Vanilloid (TRPV1) and Purine Receptors in the Mouse Neuromuscular Synapse. J Evol Biochem Phys 57, 709–719 (2021). https://doi.org/10.1134/S0022093021030182

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