Glutamine 2.0 Flashcards
For a molecule to be regarded as an NT, what must there be regarding it in the presynaptic neuron?
It itself must be present, as well as the mechanisms for its synthesis (enzymes etc)
For a molecule to be regarded as an NT, what must there be regarding it on the postsynaptic neuron?
Receptors to which the NT can bind
What are the three criteria for defining a NT?
Present in the presynaptic neuron
Capable of being released
Postsynaptic receptors to which it can bind
What kind of NT is glutamate?
An AA transmitter
What is the main excitatory NT in the CNS?
Glutamate
What is glutamate synthesised from?
Glutamine
What is glutamate reuptaken by?
Excitatory AA transporters
What other molecule can activate glutamate receptors?
Aspartate
What is excitotoxicity?
Too much signalling that leads to cell death
Where is glutamine first found in the glutamate synthesis pathway?
In glial cells
What first happens to glutamine in the glutamate synthesis pathway?
It is transported out of glial cells via glutamine transporters
Which enzyme converts glutamine to glutamate in the glutamate synthesis pathway?
Glutaminase
Where is glutaminase found?
In nerve cells
Which molecule helps glutamate be taken up into synaptic vesicles?
Vesicular glutamate transporters
In which cells are EAATs found?
Presynaptic neurons and glial cells
What are the two main classes of NT receptors?
Ionotropic and metabotropoic
What are ionitropic receptors?
Ligand gated ion channels
What type of receptor are metabotropic receptors?
G protein coupled receptors
What are the three classes of ionotropic receptor?
NMDA, AMPA, KAINATE
What are the three classes of metabotropic receptor?
Group I, Group II, Group III
What kind of ion channel does NMDA, AMPA, KAINATE all form?
tetrameric ligand gated ion channels
Which subunit must an NMDA receptor have?
GluN1
What separates the different groups of metabotropic receptors?
The second messengers they couple to
Which second messenger does Group 1 couple to?
G alpha Q
Which second messenger does Group 2 couple to?
G alpha i o
Which second messenger does group III couple to?
G alpha i o
How does glutamate bind so many receptors?
Not a rigid molecule, can adopt different conformations
What is present in the middle of the ionotropic subunits?
An ion channel pore
Which subunits of an ionotropic receptor are transmembrane?
1, 3, 4
Which segment of the subunits of an ionotropic receptor are not transmembrane?
2
Which subunit segment is facing inwards to the ion channel in a ionotropic glutamate receptor?
2
Which receptor can be homomeric?
AMPA
Which ions are an AMPA receptor permeable to?
K+ and Na+
What is the direction of K+ through an AMPA receptor?
Leaving the cell
What is the direction of Na+ through an AMPA receptor?
Entering the cell
Agonists of AMPA receptor?
glutamate, AMPA, KA
Antagonists of AMPA receptor?
NBQX (competitive), GYKI (non-competive)
What ions are NMDA receptors permeable to?
Ca2+, Na+, K+
What is the direction of K+ through an NMDA receptor?
leaving the cell
What is the direction of Ca2+ and Na+ through an NMDA receptor?
Entering the cell
What kind of gated is an NMDA receptor?
voltage and ligand
Which receptor requires a co-agonist?
NMDA
What co-agonists do an NMDA receptor require?
Glycine or serine
Why can a fast and slow time course be observed on the postsynaptic EPSP?
AMPA are fast, NMDA are slow and glutamate binds both
Meaning of a dual gating receptor?
both ligand and voltage sensitive
Which molecule blocks a NMDA receptor at resting potentian?
Mg2+
What does depolarisation do to the NMDA receptor?
Relieves the MG2+ block from the ion pore
Which ion are NMDA receptors highly permeable to?
Ca2+
WHat speed of excitation are metabotropic receptors involved in?
slow
Which molecules are NMDA receptor ion channel blockers?
Ketamine and memantine
What happens when glutamate binds to an mGluR presynaptically?
G beta gamma subunits dissociate and close a calcium ion channel (stops Ca2+ from entering), preventing release of an NT
What happens when glutamate binds to an mGluR postsynaptically?
G beta gamma subunits dissociate and close a potassium ion channel (stops K+ from leaving), leads to a slow depolarisation
What can mGluR affect in terms of calcium?
Its intracellular release
What do group 1 mGluRs do?
produce slow depolarisation and release Ca2+ from intracellular stores
What do group 2/3 mGluRs do?
Inhibit glutamate and other transmitters release
