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42 Cards in this Set

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  • Back
Four NT's to know:
Glutamate
NE
Neurotensin
Anandamide
What type is each NT?
Glutamate = Amino acid
NE = catecholamine
NT = neuropeptide
Anandamide = neuroactive lipid
Where is Glutamate primarily functional?
In the brain as the main excitatory NT
At what type of synapse does Glutamate usually operate?
At Assymetric Synapses with Primary Outflow neurons from the brain
Where is Glutamate synthesized and why?
In the brain because it can't cross the BBB
What are the precursors of Glutamate?
Intermediates in glucose metabolism.
What are the 2 ways that Glutamate is made?
1. From a-Ketoglutarate via Glutamate dehydrogenase
2. Via the Glutamine-Glutamate shuttle
What is required for Glutamate dehydrogenase action?
NADPH
What 2 enzymes are important in the glutamine-Glutamate shuttle?
Where is each found?
1. Glutaminase (neurons)
2. Glutamate synthase (astrocytes)
2 Pathways for Glutamate synthesis:
1. Glutamine/Glutamate shuttle
2. Glutamate Dehydrogenase from a-Ketoglutarate + Amino Acid
How is Glutamate released from vesicles?
By voltage-dependent opening of Calcium which allows docking and exocytosis.
How is Glutamate taken up into vesicles for storage?
By VGluT - a specific transporter
What is a nice thing about VGluT?
You can use antibodies against them to label Glutamatergic synapses.
What activates Glutamate release?
Calcium (obviously)
What inhibits Glutamate release?
Activation of Autoreceptors on the pre-synaptic neuron membrane.
What is an autoreceptor by definition?
A receptor for the same neurotransmitter released by that neuron.
What are the specific names of Glutamatergic autoreceptors?
mGluR2 and mGluR3
What is the major mechanism of inactivation of Glutamate?
Uptake via Plasma Membrane Transporters (NOT VGluT - that's only a vesicular transporter)
How does the glutamate plasma membrane transporter work?
By co-transport of Sodium
-Sodium goes down its gradient
-Glutamate goes up its gradient
Why does glutamate need a transporter?
Because it's charged.
What type of cell predominantly has Glutamate PMT?
Astrocytes - they accumulate glutamate to inactivate it, then it's converted to glutamine.
Why is it good that astrocytes accumulate Glu and convert it to Gln?
Because Glu is toxic to the brain and this is a way of converting it to something less toxic.
What are the 3 types of postsynaptic receptors for Glu?
1. Ionotropic
-NMDA
-Non-NMDA
2. Metabotropic (mGluR)
What are the 2 subtypes of non-NMDA Glutamate receptors?
1. AMPA
2. KAINATE
How do non-NMDA Glutamate receptors work?
By conducting SODIUM (mostly) and potassium causing membrane depolarization.
How are non-NMDA and NMDA receptors different?
In the cations they allow to pass thru; NMDA also allows Calcium through.
What are 6 important features to remember about NMDA receptors?
1. Very high conductance
2. Conduct Ca2+ with Na (K+)
3. Require Glycine cofactor
4. Slow Kinetics
5. Plugged by Mg2+ at resting
6. Unplugged by memb depolarzn
What is required for NMDA receptors to function?
A BIG WAVE OF GLUTAMATE ligand
-Membrane depolarization too
Why do NMDA receptors require membrane depolarization?
Because at resting Em they're plugged by Mg2+ even if thy're ligand (Glu) bound.
The whole purpose of Glu is to activate the postsynaptic neuron; how can NMDA receptors require that it ALREADY be depolarized to work?
Most Glutaminergic neurons have BOTH non-NMDA and NMDA receptors; the non-NMDA receptors generate depolarization.
What is the purpose of NMDA receptors?
The calcium influx
-helps excite the end plate
-results in kinase activation
-plays a role in memory forming and plasticity
Why is it good that NMDA receptors are so fussy and hard to activate?
Too much calcium influx into the postsynaptic neuron can be toxic.
Where are the mGluReceptors located?
-Some postsynaptic
-Some presynaptic (autoreceptors)
What are 4 effectors activated by mGluR binding?
-Ion channels
-Phospholipase C
-Adenylyl Cyclase
-Autoreceptors
Where are glutamate receptors?
At assymetric synapses on dendritic shafts and spines.
What is the functional purpose of Glutamate?
Excitatory:
-fast transmission via AMPA
-increased intracellular Ca via NMDA receptors.
At what class of synapses does Glutamate act?
Gray's Type I - Assymetric
What is a possible pathophyslgc mechanism of glutamate?
Excitotoxicity - leading to neurodegeneration.
4 Diseases associated with overactive glutamatergic systems:
-Epilepsy
-Seizures
-Huntington's disease
-ALS
So what is the primary role of:
-AMPA/Kainate receptors
-NMDA receptors
AMPA/Kainate - generate EPSPs

NMDA - allow Ca flux for kinase cascade activation, plasticity..
What is MK801?
A selective antagonist of NMDA receptors - some use in treating Huntington's and ALS
What is PCP?
Antagonist of NMDA receptors; also a drug of abuse that induces hallucinations.