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Regulation of acetylcholinesterase activity by nitric oxide in rat neuromuscular junction via N ‐methyl‐ d ‐aspartate receptor activation
Author(s) -
Petrov Konstantin A.,
Malomouzh Artem I.,
Kovyazina Irina V.,
Krejci Eric,
Nikitashina Alexandra D.,
Proskurina Svetlana E.,
Zobov Vladimir V.,
Nikolsky Evgeny E.
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12029
Subject(s) - nmda receptor , acetylcholine , neuromuscular junction , glutamate receptor , chemistry , acetylcholinesterase , neurotransmitter , synaptic cleft , nitric oxide synthase , nitric oxide , neurotransmission , biophysics , receptor , biochemistry , neuroscience , biology , pharmacology , enzyme , organic chemistry
Acetylcholinesterase ( AC hE) is an enzyme that hydrolyses the neurotransmitter acetylcholine, thereby limiting spillover and duration of action. This study demonstrates the existence of an endogenous mechanism for the regulation of synaptic AC hE activity. At the rat extensor digitorum longus neuromuscular junction, activation of N ‐methyl‐ d ‐aspartate ( NMDA ) receptors by combined application of glutamate and glycine led to enhancement of nitric oxide ( NO ) production, resulting in partial AC hE inhibition. Partial AC hE inhibition was measured using increases in miniature endplate current amplitude. AC hE inhibition by paraoxon, inactivation of NO synthase by N ω ‐nitro‐ l ‐arginine methyl ester, and NMDA receptor blockade by dl ‐2‐amino‐5‐phosphopentanoic acid prevented the increase in miniature endplate current amplitude caused by amino acids. High‐frequency (10 Hz) motor nerve stimulation in a glycine‐containing bathing solution also resulted in an increase in the amplitude of miniature endplate currents recorded during the interstimulus intervals. Pretreatment with an NO synthase inhibitor and NMDA receptor blockade fully eliminated this effect. This suggests that endogenous glutamate, released into the synaptic cleft as a co‐mediator of acetylcholine, is capable of triggering the NMDA receptor/ NO synthase‐mediated pathway that modulates synaptic AC hE activity. Therefore, in addition to well‐established modes of synaptic plasticity (e.g. changes in the effectiveness of neurotransmitter release and/or the sensitivity of the postsynaptic membrane), another mechanism exists based on the prompt regulation of AC hE activity.