Glutamatergic Transmission Flashcards
Name the neurotransmitters involved in amino acid neurotransmitter systems.
Glutamate.
Glycine.
GABA.
Briefly describe the two ways glutamate is synthesised.
- Glutamic acid, or glutamate, is synthesised during an intermediate step in the citric acid cycle by mitochondrial glutamate dehydrogenase.
- Glutamate is synthesised from glutamine by glutaminase in the CNS.
What are the three types of ionotropic glutamate receptors?
AMPA.
Kainate.
NMDA.
What are the subunits of AMPARs?
GluA1-4.
What are the subunits of kainate receptors?
GluK1-5.
What are the subtypes of NMDARs?
GluN1.
GluN2A-D.
GluN3A-B.
What are the three types of metabotropic glutamate receptors?
Group I-III.
What are the subtypes of Group I mGluRs?
mGluR1.
mGluR5.
What are the subtypes of Group II mGluRs?
mGluR2.
mGluR3.
What are the subtypes of Group III mGluRs?
mGluR4.
mGluR6.
mGluR7.
mGluR8.
When are AMPARs permeable to calcium ions?
When no GluA2 subunit is present.
What does activation of AMPARs produce?
EPSPs.
What is the role of an AMPAR?
Mediate fast excitatory neurotransmission.
Name some AMPAR agonists.
Glutamate.
AMPA.
Kainic acid.
Name some AMPAR antagonists.
CNQX.
NBQX.
What are the two primary structures of AMPARs?
Heteromeric GluA1/GluA2.
Heteromeric GluA2/GluA3.
What structure of AMPAR is usually present in small fractions?
Homomeric GluA1.
What do TARPs bind to in order to mediate postsynaptic localisation?
PSD-95.
What is palmitoylation?
Lipid modification that occurs by post-translational addition of a long-chain fatty acid to a cysteine residue.
What is the purpose of palmitoylation?
To regulate AMPA receptor trafficking.
What does TARPs stand for?
Transmembrane AMPAR regulatory proteins.
Why do TARPs associate with AMPARs?
To allow AMPARs to interact with various scaffolding proteins found in the postsynaptic density.
Name the three main scaffolding proteins found in the PSD.
PSD95.
PSD93.
SAP102.
What is the function of cell adhesion molecules?
To structurally and functionally stabilise the pre- and postsynaptic sides of the synapse.
What are the two main roles of scaffolding proteins at the PSD?
Trafficking and stabilising glutamate receptors at the synapse.
Mediating intracellular signalling stimulated by activation of the receptors.
Why are AMPARs clustered together in the synapse, directly opposite the active zone?
AMPARs have a low affinity for glutamate.
What is the purpose of the C-terminal on an AMPAR?
It is a site that allows for changes in the existing properties of AMPARs that are anchoring in the PSD.
What happens to the regulatory domains of the C-terminal of AMPARs?
They undergo posttranslational modifications, including protein phosphorylation, ubiquitination and palmitoylation.
Where has AMPAR exocytosis been observed?
At synapses.
Perisynaptic to the PSD.
On the dendritic spine.
On the spine shaft.
On the soma.
Which ions does NMDAR conduct?
Sodium.
Potassium.
Calcium.
NMDARs are either di-heteromeric or tri-heteromeric. What does this mean?
Di-heteromeric = up to two types of different subunits.
Tri-heteromeric = three types of different subunits.
What is the conventional structure of an NMDAR?
Two GluN1 subunits and two GluN2 subunits.
NMDARs have an additional co-agonist site for which molecule?
Glycine.
What is the role of the glycine binding site in NMDAR activation?
Occupancy of the glycine site is obligatory for activation of NMDARs.
Which type of molecule enhances NMDAR activation?
Endogenous polyamines, e.g. spermine.
How does zinc inhibit NMDAR action?
It can block both the channel pore and the agonist binding site.
Magnesium ions block NMDARs in a voltage-dependent manner. What does this mean?
At the RMP, the positive of the magnesium ion is attracted to the negative interior of the neuron, so it blocks the channel pore.
Which enzyme converts glutamine to glutamate in the presynaptic terminals of glutamatergic neurons?
Glutaminase.
What happens to glutamate once it has been released from nerve terminals?
It is taken up into glial cells.
What is glutamate converted into when it has been taken up into a glial cell, and by which enzyme?
It is converted into glutamine by glutamine synthetase.