Calcium-dependent phosphatase calcineurin downregulates evoked neurotransmitter release in neuromuscular junctions of mice

Gaydukov, A. E.; Tarasova, E. O.; Балезина, О. П.

doi:10.1134/s1819712413010030

Cited by 9 publications

(14 citation statements)

References 29 publications

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“…However, as it was first shown in our studies, activation of the L type calcium channels is usually accompanied by the activation of the associated ryanodine sensitive intracellular calcium stores and amplification of the cal cium signal that upregulates the Ach release [11,16].…”

Section: Resultsmentioning

confidence: 78%

“…It is known, however, that the activity of these channels can be modulated not only by adenosine receptors but by a wide range of regulators. In particular, we showed recently that calcium channels of L type are subjected to an inhibitory influence of phosphatase calcineurin [11]. Therefore, we further studied how the activity of receptors A2A facilitating the functioning of calcium channels of the L type interacts with the activity of calcineurin inhibiting these channels.…”

Section: Resultsmentioning

confidence: 98%

“…phrenicus isolated from adult (P30) male mice Electrophysiology. The dissection of muscle fibers was performed according to a standard protocol [10,11,13]; this procedure made it possible to simul taneously record the spontaneous and evoked media tor release [10,11,13]. The left part of the diaphragm with the diaphragmal nerve (n. phrenicus) was placed into a 3 mL chamber and superfused at room temper ature with an oxygenated (95% O 2 , 5% CO 2 ) Liley solution (pH 7.2-7.4) containing (in mM): NaCl, 135; KCl, 4; NaH 2 PO 4 , 0.9; CaCl 2 , 2; MgCl 2 , 1; NaHCO 3 , 16.3; glucose, 11 (all reagents from SigmaAldrich, USA).…”

Section: Methodsmentioning

confidence: 99%

“…However, as the inhibition of these channels is abolished, they are able to modulate both calcium signals and the ACh secretion [9][10][11]. Some factors and enzymes control ling functional transition of L type calcium channels from silent to active state are known [11][12][13]. How ever, the involvement of the A1 and A2A receptors and the respective signaling cascades in the evoked ACh release in motor synapses remains poorly explored.…”

Section: Introductionmentioning

confidence: 99%

“…These channels are expressed in motor ter minals but generally remain in the inactive latent state and do not influence the ACh release [7,8]. However, as the inhibition of these channels is abolished, they are able to modulate both calcium signals and the ACh secretion [9][10][11]. Some factors and enzymes control ling functional transition of L type calcium channels from silent to active state are known [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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The role of adenosine receptors and L-type calcium channels in the regulation of the mediator secretion in mouse motor synapses

Tarasova

Miteva

Gaidukov

et al. 2015

Biochem. Moscow Suppl. Ser. A

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The changes in spontaneous and evoked neurotransmitter release caused by agonists and antago nists of the A1 and A2A subtypes of adenosine receptors combined with inhibition of some enzymes and voltage dependent calcium channels of L type were studied in mouse diaphragm motor synapses using intra cellular microelectrode recordings of miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs). Simultaneous activation of presynaptic A1 and A2A receptors by endogenous adenosine during short term rhythmic activity of motor synapses was shown for the first time. Activation of receptors A1 pre vails and is followed by downregulation of the ACh release due to inhibition of intracellular cascade, which involves protein kinase A (PKA) and L type voltage dependent calcium channels. Activation of receptors A2A with their agonist CGS 21680 caused upregulation of the ACh secretion due to enhancement of PKA activity followed by activation of L type voltage dependent calcium channels. The mechanism of the evoked release potentiation, when A1 receptors are blocked or the activity of A2A receptors prevails over that of A1 receptors, involves calcium release from ryanodine sensitive intracellular calcium stores coupled with PKA and activation of L type voltage dependent calcium channels. It was found that protein phosphatase cal cineurin participates in downregulation of the L type voltage dependent calcium channels irrespective of the A1 receptors. It was shown for the first time that disinhibition of L type voltage dependent calcium channels caused by the calcineurin inhibition requires participation of the activity of A2A receptors and PKA. In con clusion, reciprocal interactions between presynaptic receptors A1 and A2A and their effect on the ACh release were shown in motor synapses. These interactions are mediated by the following cascade: PKA → L type volt age dependent calcium channels → ryanodine receptors of calcium stores. Final effect on the neurotrans mitter release depends on conditions of coactivation of these receptors and interplay of enzymes and L type voltage dependent calcium channels within synaptic terminals.

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Section: Resultsmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The role of adenosine receptors and L-type calcium channels in the regulation of the mediator secretion in mouse motor synapses

Tarasova

Miteva

Gaidukov

et al. 2015

Biochem. Moscow Suppl. Ser. A

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L-type Ca2+ Channels at Low External Calcium Differentially Regulate Neurotransmitter Release in Proximal–Distal Compartments of the Frog Neuromuscular Junction

Tsentsevitsky

Petrov

2021

Cell Mol Neurobiol

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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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Calcium-dependent phosphatase calcineurin downregulates evoked neurotransmitter release in neuromuscular junctions of mice

Cited by 9 publications

References 29 publications

The role of adenosine receptors and L-type calcium channels in the regulation of the mediator secretion in mouse motor synapses

The role of adenosine receptors and L-type calcium channels in the regulation of the mediator secretion in mouse motor synapses

L-type Ca2+ Channels at Low External Calcium Differentially Regulate Neurotransmitter Release in Proximal–Distal Compartments of the Frog Neuromuscular Junction

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

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