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Glutamate regulation of non‐quantal release of acetylcholine in the rat neuromuscular junction
Author(s) -
Malomouzh Artem I.,
Mukhtarov Marat R.,
Nikolsky Eugen E.,
Vyskočil František,
Lieberman Edward M.,
Urazaev Albert K.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01660.x
Subject(s) - nmda receptor , glutamate receptor , acetylcholine , chemistry , neuromuscular junction , long term potentiation , nitric oxide , glycine , synaptic cleft , biophysics , biochemistry , biology , endocrinology , receptor , neuroscience , amino acid
Glutamate, previously demonstrated to participate in regulation of the resting membrane potential in skeletal muscles, also regulates non‐quantal acetylcholine (ACh) secretion from rat motor nerve endings. Non‐quantal ACh secretion was estimated by the amplitude of endplate hyperpolarization (H‐effect) following blockade of skeletal muscle post‐synaptic nicotinic receptors by (+)‐tubocurarine and cholinesterase by armin (diethoxy‐ p ‐nitrophenyl phosphate). Glutamate was shown to inhibit non‐quantal release but not spontaneous and evoked quantal secretion of ACh. Glutamate‐induced decrease of the H‐effect was enhanced by glycine. Glycine alone also lowered the H‐effect, probably due to potentiation of the effect of endogenous glutamate present in the synaptic cleft. Inhibition of N ‐methyl‐ d ‐aspartate (NMDA) receptors with (+)‐5‐methyl‐10,11‐dihydro‐5 H ‐dibenzocyclohepten‐5,10‐imine (MK801), dl ‐2‐amino‐5‐phosphopentanoic acid (AP5) and 7‐chlorokynurenic acid or the elimination of Ca 2+ from the bathing solution prevented the glutamate‐induced decrease of the H‐effect with or without glycine. Inhibition of muscle nitric oxide synthase by N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME), soluble guanylyl cyclase by 1 H [1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) and binding and inactivation of extracellular nitric oxide (NO) by haemoglobin removed the action of glutamate and glycine on the H‐effect. The results suggest that glutamate, acting on post‐synaptic NMDA receptors to induce sarcoplasmic synthesis and release of NO, selectively inhibits non‐quantal secretion of ACh from motor nerve terminals. Non‐quantal ACh is known to modulate the resting membrane potential of muscle membrane via control of activity of chloride transport and a decrease in secretion of non‐quantal transmitter following muscle denervation triggers the early post‐denervation depolarization of muscle fibres.