Glutamate Flashcards
Describe the synthesis of glutamate?
- Enzyme required?
-
Glutamine—————> Glutamate
- via the use of the enzyme Glutaminase, H20 and ATP.
State the 3 different vesicular glutamate transporters?
- Locations of each?
- function?
- Results of KO in these VGLUT?
VGLUT1,VGLUT2 and VGLUT3.
- Locations:
- VGLUT1: cortex and the hippocampus.
- VGLUT2: Subcortical regions.
- VGLUT3: expressed in hippocampus and cortex; but less expressed.
VGLUT1 KO: mice survive, but begin to die after 3rd week.
VGLUT2 KO: mice die immediately after birth.
VGLUT3 KO: mice are viable but are completely deaf, as the cochlea uses glutamate via hair cells.
How are glutamate and aspartate taken up from the synaptic cleft?
- Name and state the location of each of these transporters[5 marks].
Excitatory amino acid transporters EAAT1 to EAAT5.
- EAAT1: located in the cerebellum within glial cells.
- EAAT2: located in astrocytes throughout the brain.
- EAAT3: throughout the brain, as it is the main neuronal glutamate transporter.
- EAAT4: purkinje cells in the cerebellum.
- EAAT5: present within several type of cells in the retina.
How is glutamate transported from the synaptic cleft?
- What occurs if achieved via EAAT3?
- What occurs if transported back into EAAT1 or EAAT2?
EAAT3:
- Glutamate taken up and reloaded into VGLUT.
EAAT1 or EAAT2:
- Astrocytes convert glutamate into Glutamine, via Glutamine synthase.
- when transported out of astrocytes glutaminase is used to convert it back to glutamate.
What cells use glutamate as their main neurotransmitter?
- Pyramidal neurons within the cortex.
State the ionotropic receptors for glutamate?
- AMPA receptors.
- Kainate receptors.
- NMDA receptors.
overall fast signaling.
the difference in ions transported within the 3 different types?
-
AMPA and Kainate receptors:
- flow of Na+ depolarises.
- NMDA receptors: allows both Na+ and Ca2+ to pass:
Unique characteristics of NMDA receptors?
- Flow of both Na+ and Ca2+.
- Require co-agonists with glutamate to open channel:
- Glycine or D-serine.
-
Mg2+ blocks the channel, at resting potential (-70mv).
- when depolarised, Mg2+ is dissociated.
State some non-competitive inhibitors of NMDA receptors.
- Ketamine.
- Phencyclidine(PCP).
- MK-801( dizocilpine),
State all the metabotropic glutamate receptors?
Mechanism?
-
mGluR1-mGluR8.
- G-protein,
- can inhibit c-AMP formation.
- Other activates Phosphoinositide second messenger system,(mGluR1-mGluR5).
- G-protein,
The function of L-AP4( L-2-amino-4-phosphonobutyrate)?
Function of metabotropic receptors?
-
Selective agonist for glutamate autoreceptors.
- suppressing glutamatergic synaptic transmission.
Metabotropic receptor function:
- for locomotor activity , cognition, motor coordination, mood and pain.
Clinical applications in Agonists of mGluR2?
- inhibits glutamate release in experimental animals.
- for patients with schizophrenia and neuropsychiatric disorders.
Function of Nootropics?
Function of Ampakines?
Nootropics:
- improve cognitive function.
- Acts on the cholinergic system.
- others target the glutamate receptors.
Ampakines:
- Enhance the action of AMPA receptors, by reducing rate desensitization, improving cognitive function to treat neuropsychiatric disorders.
- however no positive results on human trials.
Results of experimentation on treatment of NMDA receptor antagonists?
Results of the Doogie mouse overexpressing the NR2B subunit on the NMDA receptor?
NMDA receptor antagonists:
-
impaired spatial learning:
- as a high number of NMDA neurons in the hippocampus.
Doogie mouse, with ++NR2B on NMDA receptor:
- enhanced LTP and improved learning in memory test;
- e.g. novel recognition tasks.
