Neurotransmitters systems 1:glutamate

Question 1

What is the criteria of neurotransmitters?

Answer 1

-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

Question 2

What are the steps in action potential propagation?

Answer 2

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

Question 3

What are the steps involved in synaptic transmission?

Answer 3

• 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

Question 4

What is glutamate synthesized by?

Answer 4

Synthesised by glutamine by phosphate activated glutaminase

Question 5

Where is glutamine synthesised?

Answer 5

Synthesised in nerve terminals

Question 6

What is glutmate transported into vesicles by?

Answer 6

Transported into vesicles by VGLUT

Question 7

What is glutamate counter-transported from the vesicle by?

Answer 7

Counter transport from vesicle is with H+

Question 8

What are the 2 receptors that glutamate interacts with?

Answer 8

• Ionotropic receptors

- Metabotropic receptors

Question 9

How many classes do ionotropic receptors have and what are they?

Answer 9

3 classes:

• AMPA
• NMDA
• KAINATE

Question 10

What are all the classes of ionotropic receptors activated by?

Answer 10

All activated by glutamate and there exogenous molecule

Question 11

What does AMPA cause?

Answer 11

Influx of Na+

Efflux of K+

Question 12

What does NMDA cause?

Answer 12

Influx of Na+,Ca2+

Efflux of K+

Question 13

What does Kainate cause?

Answer 13

Influx of Na+

Efflux of K+

Question 14

What are AMPA receptors made up of?

Answer 14

Made up of 4 subunits

• GluA1
• GluA2
• GluA3
• GluA4

Question 15

How many binding sites do AMPA receptors have?

Answer 15

4 Orthosteric binding sites

Question 16

How many sites must be occupied in order for channels to open?

Answer 16

2 sites must be occupied for channel opening

Question 17

What happens to current as more binding sites are occupied?

Answer 17

Current increases as more binding sites are occupied

Question 18

What does the presence of GluA2 subunit prevent and why?

Answer 18

Presence of GluA2 subunits prevent Ca2+

-This protects against excitotoxicity

Question 19

How many subunits do NMDA receptors have and what are they?

Answer 19

Have 3 subunits

• GluN1
• GluN2
• GluN3

Question 20

What are GluN3 subunits inhibitory to?

Answer 20

GluN3 subunits are inhibitory to NMDA receptor function

Question 21

What type of gated are NMDA receptors?

Answer 21

Ligand and voltage gated
-Glutamate and glycine
Both needed in order to activate
Voltage
-Mg2+ block at resting membrane potential

Question 22

Steps involved in synaptic plasticity

Answer 22

• 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)

Question 23

What is LTP?

Answer 23

It’s persistent strengthening of synapses

Question 24

How many subunit types is Kainate receptors made up of?

Answer 24

Five subunits type:

• GluR5
• GluR6
• GluR7
• KA1
• KA2

Question 25

What type of ion channels are kainate receptors?

Answer 25

Ligand gated ion channel

Question 26

What type of receptors are metabotropic receptors?

Answer 26

Are G protein coupled receptors

Question 27

How many subtypes are metabotropic receptors made up of and why are these subtypes divided into 3 groups?

Answer 27

Made up of 8 subtypes(mGlu1-mGlu8)

The 8 subtypes are divided into 3 groups based on their sequence homology

Question 28

subtypes present in group 1

Answer 28

mGlu1

mGlu5

Question 29

subtypes present in group 2

Answer 29

mGlu2

mGlu3

Question 30

subtypes present in group 3

Answer 30

mGlu4
mGlu6
mGlu7
mGlu8

Question 31

Where are groups 1-3 subtypes found?

Answer 31

• Group 1 subtypes are present on postsynaptic membrane

- Group 2 and 3 subtypes are present on presynaptic membrane

Question 32

What are Group 1 subtypes coupled to and what does this lead to and cause?

Answer 32

Group 1 subtypes are Gq coupled

• Pip2–>DAG+IP3
• IP3R activation on ER
• Causes increase in Ca2+

Question 33

What are group 2 and 3 subtypes coupled to and what does this lead to and cause?

Answer 33

Group 2 and 3 subtypes are Gi/o coupled

• Inhibit adenylyl cyclase
• Results in decreased cAMP formation

Question 34

What do group 1 subtypes contribute to?

Answer 34

Group 1 subtypes postsynaptically contribute to LTP

Question 35

What do group 2 and 3 subtypes do?

Answer 35

Group 2 and 3 subtypes inhibit neurotransmitter release

Question 36

When does excitotoxicity occur?

Answer 36

Occurs when there’s too much excitation

Question 37

What does excessive Ca2+ cause?

Answer 37

Excessive Ca2+ causes:

• Mitochondrial damage
• Oxidative stress
• Apoptosis