ИСТИНА

PAR1 receptors (Protease-Activated Receptors type 1) have been found on postsynaptic membranes of neuromuscular junctions (NMJs), but their potential involvement in synaptic transmission has not been investigated. The mechanisms underlying the changes in spontaneous and evoked acetylcholine release caused by the activation of PAR1 by peptide agonist TRAP6 or thrombin were studied using intracellular microelectrode recordings of miniature endplate potentials (MEPPs) and multiquantal endplate potentials (EPPs) in mouse diaphragm neuromuscular preparations. The activation of PAR1 causes a sustained increase in the MEPP and EPP amplitude (but not in EPP quantal content) due to the increase in the quantal size at the presynaptic level since this effect was prevented by inhibiting of vesicular acetylcholine transport. Phospholipase C (PLC) mediates the postsynaptic signaling triggered by the PAR1 activation. The effect of PAR1 activation was mimicked by exogenously applied neurotrophin BDNF and was fully prevented by blocking the BDNF receptors (TrkB). Thus, it has been shown that the increase in acetylcholine quantal size due to the activation of PAR1 in motor synapses is mediated by a complex signaling cascade starting at the postsynaptic level of the motor synapse and finishing at the presynaptic level. It is expected that the activation of PAR1 at the muscle fiber membrane followed by the PLC up-regulation results in the release of BDNF as a retrograde signal, which, in turn, activates the presynaptic TrkB triggering the signaling cascade (without PLC participation) leading to an increase in the ACh quantal size. The work was supported by RFBR grant 16-04-00554a.