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The role of pannexin 1 in the purinergic regulation of synaptic transmission in mouse motor synapses

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

Abstract

The role of pannexin 1 in the release to the extracellular space of ATP/adenosine modulating the acetylcholine (ACh) secretion was studied in mouse diaphragm motor synapses. Using neuromuscular preparations obtained from wild-type and pannexin-1 knockout mice, the miniature endplate potential (MEPPs) and evoked endplate potentials (EPPs) were recorded in combination with pharmacological modulation of P2-type ATP receptors and A1-type adenosine receptors. Selective inhibition of A1 receptors with DPCPX or P2 receptors with PPADS increased quantal content of EPPs in wild-type mice. MRS 2211, selective antagonist of P2Y13 receptors, produced the same effect. Activation of receptors A1 or P2Y13 by their agonists (2-CADO and IDP, respectively) decreased the EPP quantal content. It means that the activity of endogenous ATP and adenosine is synergistic and directed to depression of the ACh release. ARL67156, an inhibitor of synaptic ecto-ATPases, which blocks the hydrolysis of ATP to adenosine and increases the level of ATP in the synaptic cleft, prolonged EPPs without changing their quantal content. In pannexin-1 knockout mice there were no changes in the EPP quantal content and in other parameters of synaptic transmission as compared to wildtype mice. However, downregulation of purinergic effects with antagonists of A1 or P2 receptors (DPCPX, PPADS, MRS 2211) did not change EPP quantal content and any other parameters of spontaneous or evoked ACh release in all cases. ARL67156 did not alter the temporal parameters of EPPs, either. Nevertheless, 2-CADO, the A1-type receptor agonist, decreased the EPP quantal content, while the agonist of P2Y13 receptors decreased the MEPP amplitude. Thus, in mice lacking pannexin 1, procedures revealing the presence and regulatory activity of synaptic ATP/adenosine did not change the parameters of synaptic transmission. The obtained data substantiate a mandatory role of pannexin 1 in the purinergic regulation of motor synapse activity by endogenous ATP/adenosine.

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Authors and Affiliations

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

    A. S. Miteva, A. E. Gaydukov & O. P. Balezina

  2. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 119991, Russia

    V. I. Shestopalov

Authors
  1. A. S. Miteva
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  2. A. E. Gaydukov
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  3. V. I. Shestopalov
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  4. O. P. Balezina
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Correspondence to A. E. Gaydukov.

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Original Russian Text © A.S. Miteva, A.E. Gaydukov, V.I. Shestopalov, O.P. Balezina, 2017, published in Biologicheskie Membrany, 2017, Vol. 34, No. 5, pp. 48–57.

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Miteva, A.S., Gaydukov, A.E., Shestopalov, V.I. et al. The role of pannexin 1 in the purinergic regulation of synaptic transmission in mouse motor synapses. Biochem. Moscow Suppl. Ser. A 11, 311–320 (2017). https://doi.org/10.1134/S1990747817040067

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  • DOI: https://doi.org/10.1134/S1990747817040067

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