Neuromuscular junctions glutamate receptors

To achieve their different effects NTs are not only released from different neurons to act on different receptors but their biochemistry is different. While the mechanism of their release may be similar (Chapter 4) their turnover varies. Most NTs are synthesised from precursors in the axon terminals, stored in vesicles and released by arriving action potentials. Some are subsequently broken down extracellularly, e.g. acetylcholine by cholinesterase, but many, like the amino acids, are taken back into the nerve where they are incorporated into biochemical pathways that may modify their structure initially but ultimately ensure a maintained NT level. Such processes are ideally suited to the fast transmission effected by the amino acids and acetylcholine in some cases (nicotinic), and complements the anatomical features of their neurons and the recepter mechanisms they activate. Further, to ensure the maintenance of function in vital pathways, glutamate and GABA are stored in very high concentrations (10 pmol/mg) just as ACh is at the neuromuscular junction. 

Presynaptic kainate receptors control not only the release of glutamate and GABA.. In the striatum, for instance, GluR6 activation facilitated adenosine release, which then acted onto A2A receptors to inhibit evoked GABA release, whereas spontaneous GABA release was directly facilitated via kainate receptors (Chergui et al. 2000). At neuromuscular junctions of zebrafish larvae, activation of NR2A and kainate receptors increased spontaneous acetylcholine release (Todd et al. 2004). 

Glutamate Receptors at the Drosophila Neuromuscular Junction Aaron DiAntonio... 

Berger UV, Carter RE, Coyle JT (1995) The immunocytochemical localization of IV-acetylaspartyl glutamate, its hydrolysing enzyme NAALADase, and the NMDAR-1 receptor at a vertebrate neuromuscular junction. Neuroscience 64 847-850. 

A number of invertebrate polyamine toxins have recently been shown to be open channel blockers of glutamate receptors initially at the neuromuscular junction of locusts [54] and recently on central mammalian neurones [54-57], These toxins include argiotoxin 636, Joro spider toxin and philanthotoxin. Although these polyamine toxins block NMDA receptors at least in some preparations, in others they also block responses mediated by AMPA receptors more selectively [58-60]. 

Neurotransmitters and neuropeptides Neurotransmitters are released from the presynaptic cell into the tiny volume defined by the synaptic cleft. Individual neuron contains only very small quantities of the transmitter. The released transmitter then diffuses across the cleft and binds to receptors on the post-synaptic cell. The diffusion across the short distance that separate pre- and post-synaptic neurons is fast enough to allow rapid communication between nerves or between nerve and muscle at a neuromuscular junction. acetylcholine, adrenaline noradrenaline, dopamine, serotonin, glutamate, glycine, GABA, enkephalins, substance P, angiotensin II, somatostatin... 

The chemical mediators in the central nervous system of insects are far from completely explored, but acetylcholine (ACh) and octopamine (2.35) play important roles. The neurotransmitter at insect ganglia is acetylcholine, but that at the neuromuscular junction is not acetylcholine but L-glutamic acid (Usherwood and Machili, 1968), and for this neurotransmitter, no selective antagonist has yet been found. The receptors for the neurotransmitters are well protected by selectively permeable membranes. 

Saitoe M., Tanaka S., Takata K., and Kidokoro Y. 1997. Neural activity affects distribution of glutamate receptors during neuromuscular junction formation in Drosophila embryos. Dev. Biol. 184 48-60. Salzberg A., Cohen N., Halachmi N., Kimchie Z., and Lev Z. 1993. The Drosophila Ras 2 and Rop gene pair A dual homology with a yeast Ras-like gene and a suppressor of its loss-of-function phenotype. Development 117 1309-1319. 

Figure 15.2. Drosophila larval neuromuscular junction system. A wandering third-instar larva is dissected open to reveal the ventral neuromusculature (see Figure 15.1). The peripheral nerve is severed and stimulated with a glass suction electrode. The muscle is recorded from in two-electrode voltage-clamp (TEVC) configuration. The postsynaptic excitatory junctional current (EJC) is recorded to assay synaptic transmission bottom inset). Top inset) Basis of synaptic transmission event being evoked by nerve stimulation and recorded via ion flux through muscle glutamate receptors.

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