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Open AccessArticle

Regulation of Acetylcholine Quantal Release by Coupled Thrombin/BDNF Signaling in Mouse Motor Synapses

Department of Human & Animal Physiology, Lomonosov Moscow State University, Leninskie Gory 1/12, 119991 Moscow, Russia
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Author to whom correspondence should be addressed.
Cells 2019, 8(7), 762; https://doi.org/10.3390/cells8070762
Received: 30 June 2019 / Revised: 13 July 2019 / Accepted: 22 July 2019 / Published: 22 July 2019
The aim of this study was to compare the acute effects of thrombin and brain-derived neurotrophic factor (BDNF) on spontaneous miniature endplate potentials (MEPPs) and multiquantal evoked endplate potentials (EPPs) in mouse neuromuscular junctions (NMJs) of m. diaphragma and m. EDL. Intracellular microelectrode recordings of MEPPs and EPPs were used to evaluate the changes in acetylcholine (ACh) release in mature and newly-formed mouse NMJs. Thrombin (1 nM) increased the amplitude of MEPPs and EPPs by 25–30% in mature and newly-formed NMJs. This effect was due to an enhanced loading of synaptic vesicles with ACh and increase of ACh quantal size, since it was fully prevented by blocking of vesicular ACh transporter. It was also prevented by tropomyosin-related kinase B (TrkB) receptors inhibitor ANA12. Exogenous BDNF (1 nM) mimicked thrombin effect and increased the amplitude of MEPPs and EPPs by 25–30%. It required involvement of protein kinase A (PKA) and mitogen-activated protein kinase (MEK1/2)-mediated pathway, but not phospholipase C (PLC). Blocking A2A adenosine receptors by ZM241385 abolished the effect of BDNF, whereas additional stimulation of A2A receptors by CGS21680 increased MEPP amplitudes, which was prevented by MEK1/2 inhibitor U0126. At mature NMJs, BDNF enhanced MEPPs frequency by 30–40%. This effect was selectively prevented by inhibition of PLC, but not PKA or MEK1/2. It is suggested that interrelated effects of thrombin/BDNF in mature and newly-formed NMJs are realized via enhancement of vesicular ACh transport and quantal size increase. BDNF-induced potentiation of synaptic transmission involves the functional coupling between A2A receptor-dependent active PKA and neurotrophin-triggered MAPK pathway, as well as PLC-dependent increase in frequency of MEPPs. View Full-Text
Keywords: endplate potentials; neuromuscular junction; thrombin; BDNF; TrkB; MEK1/2; A2A receptors; PKA; PLC endplate potentials; neuromuscular junction; thrombin; BDNF; TrkB; MEK1/2; A2A receptors; PKA; PLC
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Gaydukov, A.; Bogacheva, P.; Tarasova, E.; Molchanova, A.; Miteva, A.; Pravdivceva, E.; Balezina, O. Regulation of Acetylcholine Quantal Release by Coupled Thrombin/BDNF Signaling in Mouse Motor Synapses. Cells 2019, 8, 762.

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