Glutamate (FS - Week 2) Flashcards
What type of neurotransmitter is glutamate
excitatory
Where is glutamate synthesised?
in the nerve terminals
What is the name of the enzyme that converts glutamine to glutamate?
Glutaminase
What is the name of the transporter that transports glutamate into vesicles?
VGLUT
What is the name of the transporter that reuptakes glutamate into neurons and glial cells
EAAT
What is the name of the enzyme that degrades glutamate to glutamine
glutamine synthase
What is the name of the transporter on Glial cells?
SN1
What is the name of transporters on neurons?
SAT2
Name the 3 ionotropic glutamate receptors
- AMPA receptors
- NMDA receptors
- Kainate receptors
Name the 3 metabotropic glutamate receptors
- Group I
- Group II
- Group III
How is the NMDA receptor different in terms of influx of ions to the AMPA and Kainate receptors?
- it allows the influx of Na+ and Ca2+ whereas the AMPA receptor only allows Na+ influx
How many subtypes of AMPA receptors are there?
4
- GluA1
- GluA2
- GluA3
- GluA4
How many binding sites are there on the AMPA receptor?
4
How many sites of the AMPA receptor need to be occupied for the channel to open?
2
What subtype stops the influx of Ca2+ and what does this prevent?
GluA2
prevents excitotoxicity
How many subunit types are there of the NMDA receptor
- GluN1
- GluN2
- GluN3
What is the typical composition of an NMDA receptor
2 GluN1 and 2 GluN2/3
What subtype is inhibitory in the NMDA receptor function
GluN3
Apart from influx of ions, what makes the NMDA receptor different to the other glutamate receptors?
ligand-gated ion channel and a voltage-gated ion channel
What subunits does glutamate bind to on the NMDA receptor
GluN2
How many subtypes of the Kainate receptor are there?
5
- GluK1 > 5
How many subtypes of metabotropic glutamate receptors are there?
8
mGlu1-8
Describe 3 features of the group 1 metabotropic receptors
- located post synaptically
- Gq coupled = increase in Ca2+
- include subtypes mGlu1 and mGlu5
Describe 3 features of the group 2 metabotropic receptors
- located pre synaptically
- Gi/o coupled = NT inhibited release
- include subtypes mGlu2 and mGlu3
Describe 3 features of the group 3 metabotropic receptors
- located pre synaptically
- Gi/o coupled = NT inhibited release
- include subtypes mGlu4/6/7/8
What is meant by excitatory postsynaptic current
the flow of ions and current across a postsynaptic membrane
How do excitatory postsynaptic currents increase the likelihood of an action potential firing
they lead to excitatory postsynaptic potentials
Why are EPSCs slower and longer in NMDA and kainate receptors than AMPA receptors
AMPA receptors are the primary mediators of excitatory neurotransmission
What is excitotoxicity
excessive excitatory stimulation can lead to neuronal damage and death
How does excitotoxicity lead to neuronal damage
- damage to vesicular glutamate transporters = build up of glutamate in presynaptic neuron
- EAATs reverse their function and pump glutamate into the synaptic cleft (it is released without AP firing)
- postsynaptic AMPA NMDA receptors are activated = influx of Ca2+ into postsynaptic neuron in an uncontrolled manner
What are the consequences of excessive Ca2+
- mitochondrial damage
- oxidative stress
- apoptosis
Name a disease excitotoxicity can lead to
Alzheimer’s
What is Alzheimer’s disease and name a drug used in the treatment of alzheimer’s.
Neuronal cell death in the hippocampus
Memantine - an NMDA receptor antagonist - blocks NMDA receptor ion channel which decreases glutamate neurotoxicity
What is meant by long term potentiation
persistent strengthening of a synapse based upon repeated patterns of activity
Describe initial phase long-term potentiation mechanism of action
- glutamate activates AMPA receptors - Na+ influx into postsynaptic neuron = depolarisation
- NMDA receptors open due to depolarisation which removes the Mg2+ ion from blocking voltage gated ion channel
- Ca2+ ions enter - activates postsynaptic protein kinases (CaMKII and PKC)
- these lead to insertion of new AMPA receptors at postsynaptic membrane = increase sensitivity to glutamate = increased ion channel conductance
