Neurotransmitters systems 1:glutamate Flashcards
What is the criteria of neurotransmitters?
-Molecule must be synthesized and stored in presynaptic neuron
-Molecule must be released by the presynaptic axon
terminal upon stimulation
-Molecule must produce a response in the postsynaptic cell
What are the steps in action potential propagation?
At rest:
-Voltage gated sodium and potassium channels are closed
Depolarization
-A stimulus causes voltage gated sodium channels to open
-This causes an influx of Na+ inside the cells increasing the depolarization
Falling phase of action potential
-Na+ channels are deactivated by being plugged and voltage gated potassium open
-Inside of cell becomes more negative
Undershoot
-Voltage gated K+ remain open a bit too long causing hyperpolarisation
-Na+/K+ ATP pump activated to reach resting potential
What are the steps involved in synaptic transmission?
- Action potential arrives at synaptic bouton
- Voltage gated Ca2+ channels open and there’s an influx of Ca2+ into the bouton
- There’s increased [Ca2+]i which initiates vesicle fusion with the presynaptic membrane
What is glutamate synthesized by?
Synthesised by glutamine by phosphate activated glutaminase
Where is glutamine synthesised?
Synthesised in nerve terminals
What is glutmate transported into vesicles by?
Transported into vesicles by VGLUT
What is glutamate counter-transported from the vesicle by?
Counter transport from vesicle is with H+
What are the 2 receptors that glutamate interacts with?
- Ionotropic receptors
- Metabotropic receptors
How many classes do ionotropic receptors have and what are they?
3 classes:
- AMPA
- NMDA
- KAINATE
What are all the classes of ionotropic receptors activated by?
All activated by glutamate and there exogenous molecule
What does AMPA cause?
Influx of Na+
Efflux of K+
What does NMDA cause?
Influx of Na+,Ca2+
Efflux of K+
What does Kainate cause?
Influx of Na+
Efflux of K+
What are AMPA receptors made up of?
Made up of 4 subunits
- GluA1
- GluA2
- GluA3
- GluA4
How many binding sites do AMPA receptors have?
4 Orthosteric binding sites
How many sites must be occupied in order for channels to open?
2 sites must be occupied for channel opening
What happens to current as more binding sites are occupied?
Current increases as more binding sites are occupied
What does the presence of GluA2 subunit prevent and why?
Presence of GluA2 subunits prevent Ca2+
-This protects against excitotoxicity
How many subunits do NMDA receptors have and what are they?
Have 3 subunits
- GluN1
- GluN2
- GluN3
What are GluN3 subunits inhibitory to?
GluN3 subunits are inhibitory to NMDA receptor function
What type of gated are NMDA receptors?
Ligand and voltage gated -Glutamate and glycine Both needed in order to activate Voltage -Mg2+ block at resting membrane potential
Steps involved in synaptic plasticity
- Neurotransmitter binds to AMPAR
- This causes depolarisation of the post-synaptic memrbane
- This leads to the Mg2+ block leaving the NMDAR which allows a futher influx of Ca2+ and K+ causing further depolarisation
- Ca2+ causes more making and postage of AMPAR receptors to the post synaptic membrane
- Ca2+ activates CamKII which phosphorylates AMPAR receptors allowing more ions to pass through AMPAR receptors
- This results in long term potentiation(LTP)
What is LTP?
It’s persistent strengthening of synapses
How many subunit types is Kainate receptors made up of?
Five subunits type:
- GluR5
- GluR6
- GluR7
- KA1
- KA2
What type of ion channels are kainate receptors?
Ligand gated ion channel
What type of receptors are metabotropic receptors?
Are G protein coupled receptors
How many subtypes are metabotropic receptors made up of and why are these subtypes divided into 3 groups?
Made up of 8 subtypes(mGlu1-mGlu8)
The 8 subtypes are divided into 3 groups based on their sequence homology
subtypes present in group 1
mGlu1
mGlu5
subtypes present in group 2
mGlu2
mGlu3
subtypes present in group 3
mGlu4
mGlu6
mGlu7
mGlu8
Where are groups 1-3 subtypes found?
- Group 1 subtypes are present on postsynaptic membrane
- Group 2 and 3 subtypes are present on presynaptic membrane
What are Group 1 subtypes coupled to and what does this lead to and cause?
Group 1 subtypes are Gq coupled
- Pip2–>DAG+IP3
- IP3R activation on ER
- Causes increase in Ca2+
What are group 2 and 3 subtypes coupled to and what does this lead to and cause?
Group 2 and 3 subtypes are Gi/o coupled
- Inhibit adenylyl cyclase
- Results in decreased cAMP formation
What do group 1 subtypes contribute to?
Group 1 subtypes postsynaptically contribute to LTP
What do group 2 and 3 subtypes do?
Group 2 and 3 subtypes inhibit neurotransmitter release
When does excitotoxicity occur?
Occurs when there’s too much excitation
What does excessive Ca2+ cause?
Excessive Ca2+ causes:
- Mitochondrial damage
- Oxidative stress
- Apoptosis
