Glutamate regulation of non‐quantal release of acetylcholine in the rat neuromuscular junction

• Published in: Journal of neurochemistry 2003-04, Vol.85 (1), p.206-213
• Main Authors: Malomouzh, Artem I., Mukhtarov, Marat R., Nikolsky, Eugen E., Vyskočil, František, Lieberman, Edward M., Urazaev, Albert K.
• Format: Article
• Language: English
• Subjects: Acetylcholine - metabolism; Animals; Calcium - metabolism; Cholinesterase Inhibitors - pharmacology; Electrophysiology; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Glutamic Acid - metabolism; Glutamic Acid - pharmacology; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; muscle endplate; Muscle, Skeletal - innervation; Muscle, Skeletal - metabolism; Neuromuscular Junction - drug effects; Neuromuscular Junction - metabolism; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide - pharmacology; non‐vesicular transmitter; N‐methyl‐d‐aspartate receptor; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate - agonists; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2003.01660.x

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‐5H‐dibenzocyclohepten‐5,10‐imine (MK801), dl‐2‐amino‐5‐phosphopentanoic acid (AP5) and 7‐chlorokynurenic acid or the elimination of Ca2+ from the bathing solution prevented the glutamate‐induced decrease of the H‐effect with or without glycine. Inhibition of muscle nitric oxide synthase by NG‐nitro‐l‐arginine methyl ester (l‐NAME), soluble guanylyl cyclase by 1H[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.