Neurotransmitter Systems I : Glutamate

Question 1

What occurs at synapses?

Answer 1

→ Synaptic transmission

→ Electrical → chemical → electrical

Question 2

What are the 3 criteria for being a neurotransmitter?

Answer 2

→ Molecule must be synthesized and stored in the presynaptic neuron - for fast transmission
→ Molecule must be released by the presynaptic axon terminal upon stimulation
→ Must produce a response in the postsynaptic cells

Question 3

How do vesicles fuse to the membrane?

Answer 3

→ Change in voltage when AP occurs
→ Activates voltage gated Ca2+ channels 
→ Calcium rushes into the cell 
→ Activates the proteins on the vesicles
→ Signals to fuse to the synaptic membrane

Question 4

Describe action potential propagation

Answer 4

1) At rest the voltage gated K+ and Na+ channels are closed
2) There is a depolarising stimulus
3) this activates the voltage gated Na+ channels in the membrane
4) further Na+ influx and more depolarisation
5) At the top of the peak (~ +40mv) the Na+ channels are deactivated by plugging
6) No further influx of Na+ into the cell
7) The voltage gated K+ channels are activated and opened
8) K+ flows out of the membrane down its gradient
9) Voltage decreases
10) K+ channels are open for a bit too long so it hyperpolarises
11) Na+/K+ pump restores the resting potential

Question 5

Why can the action potential only travel one way?

Answer 5

→ The sodium channels are plugged

→ Na+ can only move forwards

Question 6

What are the 4 main neurotransmitters?

Answer 6

→ ACh
→ Glutamate
→ GABA
→ Glycine

Question 7

What are amino acid neurotransmitters?

Answer 7

→ GABA
→ glutamate
→ glycine

Question 8

Why are amino acid neurotransmitters called that?

Answer 8

→ their precursors are amino acids

Question 9

How is glutamine turned into glutamate?

Answer 9

→ phosphate activated glutaminase

→ Amine group gets substituted by an oxygen

Question 10

Where is glutamate synthesized?

Answer 10

→ In the nerve terminals

Question 11

Describe how glutamate gets packaged into vesiscles

Answer 11

1) Glutamate is packed in the vesicles by vesicular glutamate transporter
2) It is counter transported with H+ ions
3) The intracellular environment of vesicles is very acidic so the H+ want to diffuse down their gradient
4) the transporter moves H+ out and glutamate in

Question 12

Where is the AMPA receptor found?

Answer 12

→ Post synaptically

Question 13

What are the 3 ionotropic receptors for glutamate?

Answer 13

→ AMPA
→ NMDA
→ Kainate

Question 14

Why do the ionotropic receptors for glutamate have those names?

Answer 14

→ They all have the endogenous agonist glutamate

→ They can be activated by exogenous compounds

Question 15

What are the 4 subunit types of AMPA receptors?

Answer 15

→ GluA1
→ GluA2
→ GluA3
→GluA4

Question 16

What are the AMPA receptors composed of and what kind of receptor are they?

Answer 16

→ tqo GluA2 subunits
→ and two GluA1, 3 or 4
→ hetero-tetrameric

Question 17

How many binding sites does the AMPA receptor have and how many must be occupied for channel opening?

Answer 17

→ 4 orthosteric binding sites

→ Two sites must be occupied for channel opening

Question 18

What happens to an AMPA receptor as more binding sites are occupied?

Answer 18

→ Current increases

Question 19

What protects against excitotoxicity in AMPA receptors?

Answer 19

→ Presence of GluA2 subunits prevent Ca2+ flow

Question 20

What are the 3 subunit types of NMDA receptors?

Answer 20

→ GluN1
→ GluN2
→ GluN3

Question 21

What are NMDA receptors composed of and what kind of a receptor are they ?

Answer 21

→ two GluN1 subunits
→ two GluN2 or GluN3
→ heterotetrameric

Question 22

What are the ligands for an NMDA receptor?

Answer 22

→ Glutamate
→ glycine
→ D-serine

Question 23

How do GluN3 subunits affect NMDA?

Answer 23

→ they are inhibitory

Question 24

What ion is important in synaptic plasticity?

Answer 24

→ Mg2+ block

Question 25

Describe the process of synaptic plasticity

Answer 25

1) action potential
2) causes a graded potential of a certain size
3) The neurotransmitter binds to the AMPA receptors
4) it depolarises the synaptic cell
5) causes the Mg2+ block to leave the NMDA receptors
6) activates NMDA which further depolarises the cell
7) influx of Na+ and Ca2+
8) Ca2+ influx causes the cell to make and traffic more AMPA receptors to the membrane
9) There is an even larger depolarisation
10) Ca2+ activates CAM kinase II which phosphorylates AMPA receptors
11) allows AMPA to pass more current per channel opening and increases the permeability of AMPA receptors
12) The changes in membrane persist for a number of hours and days

Question 26

What are the 5 subunits of kainate receptors?

Answer 26

→ GluR5
→ GluR6b
→ GluR7
→ KA1 
→ KA2

Question 27

What is excitotoxicity and what happens as a resulf of this?

Answer 27

→ too much excitation 
→ damage to functioning of vesicular glutamate transporters
→ lots of glutamate in the cytosol
→ no gradient for transporters
→ glutamate is pumped out of the cell
→ released without stimulus

Question 28

What are the effects of excitotoxicity?

Answer 28

→ mitochondrial damage
→ Oxidative stress
→ Apoptosis
→ Stroke
→ Autism & Alzheimers

Question 29

What type of receptors are metabotropic?

Answer 29

→ G couples receptors

Question 30

How many types of metabotropic receptor are there for glutamate?

Answer 30

→ 8 types

Question 31

What are the 3 subtypes of glutamate receptor?

Answer 31

→ 1 - MGlu1 and MGlu5
→ 2- MGlu2 and Mglu 3
→ 3 - MGlu 4, MGlu 6, MGlu 7, MGlu 8

Question 32

What type of G protein receptor are the group 1 subtype receptors?

Answer 32

→ Gq

Question 33

What type of G protein receptor are the group 2 and 3 subtype receptors?

Answer 33

→ Gi

Question 34

Where are the group 1 G protein subtype receptors found?

Answer 34

→ post synaptically

Question 35

Where are the group 2 and 3 G protein subtype receptors found?

Answer 35

→ Presynaptically

Question 36

What kind of a neurotransmitter is glutamate?

Answer 36

→ Excitatory

Question 37

What are the domains that make up a G protein?

Answer 37

→ Venus flytrap domain
→ 7 transmembrane domain
→cysteine rich domain
→ C terminus domain

Question 38

How can excitotoxicity be stopped?

Answer 38

→ memantine

→ a low affinity NMDA receptor