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

Miteva, A. S.; Gaydukov, A. E.; Shestopalov, Valery I.; Балезина, О. П.

doi:10.1134/s1990747817040067

Cited by 9 publications

(10 citation statements)

References 26 publications

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“…We reasoned that the lack of Panx1 may induce changes in the concentrations of ATP and its derivatives in the synaptic cleft [28], which in turn may help with evaluating P2X7-induced effects on synaptic transmission. In support of this hypothesis, we have recently found that knockout of Panx1 does not induce any changes in quantal ACh release by itself, but it alters its purinergic modulation in NMJs [15].…”

Section: Resultsmentioning

confidence: 66%

“…Second, signaling cascades in motor nerve terminals are triggered by various presynaptic receptors during evoked synaptic activity. For this latter reason, the effects of activation of P2X7 receptors by endogenous ATP can be masked by concurrent inhibition of ACh release mediated by metabotropic A 1 and P2Y13 receptors [14,15,26,29] or by muscarinic receptors [32]. To test this hypothesis, we used Panx1 −/− NMJs in further experiments, since our recent results have shown that in the absence of Panx1, the activation of presynaptic A 1 and P2Y13 receptors by endogenous adenosine or ATP was abolished, leading to the disappearance of purinergic inhibition of synaptic transmission [15].…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that the experimental approach utilizing Panx1 −/− mice and short-term rhythmic stimulation of motor synapses makes it possible to exclude the activation of many (if not all) inhibitory ATP and adenosine receptors by their endogenous ligands [15]. Thus, in the absence of inhibitory A 1 and P2Y13 receptor activity, it became possible to observe (in pure form) the potentiation of ACh release caused by selective activation of P2X7 receptors by their exogenous agonist and to reveal the mechanism of P2X7-induced increase in synaptic transmission at motor synapses with the participation of activated СaM, CaMKII, and L-type VDCCs.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we demonstrated that the suppression of evoked ACh release, mediated by presynaptic A 1 and P2Y13 receptors, depends strictly on the presence of the membrane channel protein pannexin 1 (Panx1), which acts as a synaptic ATP/ adenosine supplier. At NMJs of Panx1 −/− mice, which lack endogenous ATP/adenosine delivery to the synaptic cleft via Panx1 channels, the A 1 -and P2Y13 receptor-mediated inhibition of evoked ACh release was completely abolished [15]. Possible alterations in neuromuscular synaptic transmission due to activation of P2X7 receptors under these conditions remain to be elucidated.…”

Section: Introductionmentioning

confidence: 95%

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Mechanism of P2X7 receptor-dependent enhancement of neuromuscular transmission in pannexin 1 knockout mice

Miteva

Gaydukov

Shestopalov

et al. 2018

Purinergic Signalling

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P2X7 receptors are present in presynaptic membranes of motor synapses, but their regulatory role in modulation of neurotransmitter release remains poorly understood. P2X7 receptors may interact with pannexin 1 channels to form a purinergic signaling unit. The potential mechanism of P2X7 receptor-dependent modulation of acetylcholine (ACh) release was investigated by recording miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) in neuromuscular junctions of wildtype (WT) and pannexin 1 knockout (Panx1 −/−) mice. Modulation of P2X7 receptors with the selective inhibitor A740003 or the selective agonist BzATP did not alter the parameters of either spontaneous or evoked ACh release in WT mice. In Panx1 −/− mice, BzATP-induced activation of P2X7 receptors resulted in a uniformly increased quantal content of EPPs during a short stimulation train. This effect was accompanied by an increase in the size of the readily releasable pool, while the release probability did not change. Inhibition of calmodulin by W-7 or of calcium/calmodulin-dependent kinase II (CaMKII) by KN-93 completely prevented the potentiating effect of BzATP on the EPP quantal content. The blockade of L-type calcium channels also prevented BzATP action on evoked synaptic activity. Thus, the activation of presynaptic P2X7 receptors in mice lacking pannexin 1 resulted in enhanced evoked ACh release. Such enhanced release was provoked by triggering the calmodulin-and CaMKIIdependent signaling pathway, followed by activation of presynaptic L-type calcium channels. We suggest that in WT mice, this pathway is downregulated due to pannexin 1-dependent tonic activation of inhibitory presynaptic purinergic receptors, which overcomes P2X7-mediated effects.

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Section: Resultsmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Mechanism of P2X7 receptor-dependent enhancement of neuromuscular transmission in pannexin 1 knockout mice

Miteva

Gaydukov

Shestopalov

et al. 2018

Purinergic Signalling

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“…We previously showed that the supply of endogenous ATP/adenosine to the synaptic terminals via pannexin-1 hemichannels and the activation of various presynaptic purinoreceptors is abolished at the NMJs of Panx1 −/− mice. Pannexin-1 knockout is primarily followed by a lack of activation of metabotropic A1-and P2Y13 receptors, which inhibit (silence) L-type VDCCs and their coupling to ACh secretion [10,17]. As a result, in the NMJs of Panx1 −/− mice, the activation of P2X7 receptor function by BzATP becomes more pronounced and is accompanied by the activation of presynaptic CaMKII, leading to the potentiation of ACh secretion due to the activation of L-type VDCCs, which can be blocked by nitrendipine [10].…”

Section: Discussionmentioning

confidence: 99%

Interaction between Calcium Chelators and the Activity of P2X7 Receptors in Mouse Motor Synapses

Miteva

Gaydukov

Балезина

2020

IJMS

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The ability of P2X7 receptors to potentiate rhythmically evoked acetylcholine (ACh) release through Ca2+ entry via P2X7 receptors and via L-type voltage-dependent Ca2+ channels (VDCCs) was compared by loading Ca2+ chelators into motor nerve terminals. Neuromuscular preparations of the diaphragms of wild-type (WT) mice and pannexin-1 knockout (Panx1−/−) mice, in which ACh release is potentiated by the disinhibition of the L-type VDCCs upon the activation of P2X7 receptors, were used. Miniature end-plate potentials (MEPPs) and evoked end-plate potentials (EPPs) were recorded when the motor terminals were loaded with slow or fast Ca2+ chelators (EGTA-AM or BAPTA-AM, respectively, 50 μM). In WT and Panx1−/− mice, EGTA-AM did not change either spontaneous or evoked ACh release, while BAPTA-AM inhibited synaptic transmission by suppressing the quantal content of EPPs throughout the course of the short rhythmic train (50 Hz, 1 s). In the motor synapses of either WT or Panx1−/− mice in the presence of BAPTA-AM, the activation of P2X7 receptors by BzATP (30 μM) returned the EPP quantal content to the control level. In the neuromuscular junctions (NMJs) of Panx1−/− mice, EGTA-AM completely prevented the BzATP-induced increase in EPP quantal content. After Panx1−/− NMJs were treated with BAPTA-AM, BzATP lost its ability to enhance the EPP quantal content to above the control level. Nitrendipine (1 μM), an inhibitor of L-type VDCCs, was unable to prevent this BzATP-induced enhancement of EPP quantal content to the control level. We propose that the activation of P2X7 receptors may provide additional Ca2+ entry into motor nerve terminals, which, independent of the modulation of L-type VDCC activity, can partially reduce the buffering capacity of Ca2+ chelators, thereby providing sufficient Ca2+ signals for ACh secretion at the control level. However, the activity of both Ca2+ chelators was sufficient to eliminate Ca2+ entry via L-type VDCCs activated by P2X7 receptors and increase the EPP quantal content in the NMJs of Panx1−/− mice to above the control level.

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Pannexin1 channels regulate mechanically stimulated but not spontaneous adenosine release

2022

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

Cited by 9 publications

References 26 publications

Mechanism of P2X7 receptor-dependent enhancement of neuromuscular transmission in pannexin 1 knockout mice

Mechanism of P2X7 receptor-dependent enhancement of neuromuscular transmission in pannexin 1 knockout mice

Interaction between Calcium Chelators and the Activity of P2X7 Receptors in Mouse Motor Synapses

Pannexin1 channels regulate mechanically stimulated but not spontaneous adenosine release

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