Page last updated: 2024-10-24

glutamate secretion, neurotransmission

Definition

Target type: biologicalprocess

The controlled release of glutamate by a cell, in which the glutamate acts as a neurotransmitter. [GOC:dph]

Glutamate secretion, a crucial process in neuronal communication, involves a complex interplay of intracellular signaling pathways, vesicle trafficking, and membrane fusion. Here's a detailed breakdown:

1. **Glutamate Synthesis and Packaging:**
- Glutamate, the primary excitatory neurotransmitter in the central nervous system, is synthesized from glutamine by the enzyme glutaminase within presynaptic neurons.
- Synthesized glutamate is then actively transported into synaptic vesicles, small membrane-bound sacs that store neurotransmitters. This transport is mediated by vesicular glutamate transporters (VGLUTs), ensuring high concentrations of glutamate within the vesicles.

2. **Action Potential Arrival and Calcium Influx:**
- When an action potential arrives at the presynaptic terminal, it triggers the opening of voltage-gated calcium channels.
- Calcium ions (Ca2+) rapidly influx into the presynaptic terminal, acting as a critical signal for neurotransmitter release.

3. **Vesicle Docking and Fusion:**
- The influx of Ca2+ initiates a cascade of molecular events leading to the fusion of glutamate-filled vesicles with the presynaptic membrane.
- Synaptotagmin, a Ca2+-binding protein, plays a key role in this process by sensing Ca2+ levels and mediating vesicle docking and fusion.
- Other proteins, including SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), also contribute to the precise docking and fusion of vesicles with the presynaptic membrane.

4. **Glutamate Release into Synaptic Cleft:**
- Upon fusion, the vesicle membrane merges with the presynaptic membrane, releasing glutamate into the synaptic cleft, the narrow space between the presynaptic and postsynaptic neurons.
- This release of glutamate is a rapid and highly regulated process, ensuring precise neurotransmission.

5. **Glutamate Receptor Activation:**
- Glutamate released into the synaptic cleft binds to glutamate receptors on the postsynaptic neuron.
- These receptors, including AMPA, NMDA, and kainate receptors, are ionotropic, meaning they directly open ion channels upon glutamate binding.
- This opening allows ions like sodium and calcium to flow into the postsynaptic neuron, triggering an excitatory postsynaptic potential (EPSP) and ultimately contributing to neuronal signaling.

6. **Glutamate Clearance and Recycling:**
- To ensure precise and efficient neurotransmission, glutamate is rapidly removed from the synaptic cleft after release.
- This removal is achieved by glutamate transporters, which actively transport glutamate back into presynaptic neurons or into surrounding glial cells.
- Glial cells can then convert glutamate back into glutamine, which is transported back to presynaptic neurons, completing the cycle.

7. **Regulation of Glutamate Secretion:**
- Glutamate secretion is tightly regulated by various mechanisms, including presynaptic autoreceptors, feedback loops, and intracellular signaling pathways.
- These mechanisms ensure that glutamate release occurs at appropriate levels and in response to specific neuronal activity, preventing excessive excitation or neurotoxicity.'
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Proteins (2)

ProteinDefinitionTaxonomy
ATP-sensitive inward rectifier potassium channel 8An ATP-sensitive inward rectifier potassium channel 8 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q15842]Homo sapiens (human)
ATP-binding cassette sub-family C member 8An ATP-binding cassette sub-family C member 8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q09428]Homo sapiens (human)

Compounds (17)

CompoundDefinitionClassesRoles
diazoxidediazoxide : A benzothiadiazine that is the S,S-dioxide of 2H-1,2,4-benzothiadiazine which is substituted at position 3 by a methyl group and at position 7 by chlorine. A peripheral vasodilator, it increases the concentration of glucose in the plasma and inhibits the secretion of insulin by the beta- cells of the pancreas. It is used orally in the management of intractable hypoglycaemia and intravenously in the management of hypertensive emergencies.

Diazoxide: A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.
benzothiadiazine;
organochlorine compound;
sulfone
antihypertensive agent;
beta-adrenergic agonist;
bronchodilator agent;
cardiotonic drug;
diuretic;
K-ATP channel agonist;
sodium channel blocker;
sympathomimetic agent;
vasodilator agent
glyburideglyburide : An N-sulfonylurea that is acetohexamide in which the acetyl group is replaced by a 2-(5-chloro-2-methoxybenzamido)ethyl group.

Glyburide: An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide
monochlorobenzenes;
N-sulfonylurea
anti-arrhythmia drug;
EC 2.7.1.33 (pantothenate kinase) inhibitor;
EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor;
hypoglycemic agent
troglitazoneTroglitazone: A chroman and thiazolidinedione derivative that acts as a PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) agonist. It was formerly used in the treatment of TYPE 2 DIABETES MELLITUS, but has been withdrawn due to hepatotoxicity.chromanes;
thiazolidinone
anticoagulant;
anticonvulsant;
antineoplastic agent;
antioxidant;
EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
hypoglycemic agent;
platelet aggregation inhibitor;
vasodilator agent
n-cyano-n'-(1,1-dimethylpropyl)-n''-(3-pyridinyl)guanidineN-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine: potassium channel openerpyridines
repaglinidepiperidines
cromakalimCromakalim: A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)
rosiglitazoneaminopyridine;
thiazolidinediones
EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
insulin-sensitizing drug
mk 7675-((2,4-dioxo-5-thiazolidinyl)methyl)-2-methoxy-N-((4-(trifluoromethyl)phenyl)methyl)benzamide: an antihyperlipidemic agent that also functions as an insulin sensitizer, PPARalpha agonist, and PPARgamma agonist; structure in first source
zeneca zd 6169Zeneca ZD 6169: an ATP-sensitive potassium channel opener; structure given in first source
cromakalim1-benzopyran
clamikalantclamikalant: inhibits ATP-sensitive potassium channel; structure in first source
zm226600ZM226600: an ATP-sensitive potassium channel opener; structure in first sourceanilide
way 133537
ly 465608LY 465608: a nonthiazolidinedione agonist of both PPAR-alpha and PPAR-gamma of Ligand Pharm. and Eli Lilly
bm 131246
nn 414NN 414: a hypoglycemic agent with insulin release modulating and potassium channel activating activities; structure in first source
7-chloro-3-isopropylamino-4h-1,2,4-benzothiadiazine 1,1-dioxide7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide: activates ATP-sensitive potassium channels; structure in first source