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πš™πš‘πš’πšœπš’πš˜πš•πš˜πšπš’ 𝟸 : πš—πšŽπšžπš›πš˜πšœπšŒπš’πšŽπš—πšŒπšŽ > Neurotransmitter Systems I : Glutamate > Flashcards

Neurotransmitter Systems I : Glutamate Flashcards

1
Q

What occurs at synapses?

A

β†’ Synaptic transmission

β†’ Electrical β†’ chemical β†’ electrical

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2
Q

What are the 3 criteria for being a neurotransmitter?

A

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

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3
Q

How do vesicles fuse to the membrane?

A 
β†’ Change in voltage when AP occurs
β†’ Activates voltage gated Ca2+ channels 
β†’ Calcium rushes into the cell 
β†’ Activates the proteins on the vesicles
β†’ Signals to fuse to the synaptic membrane
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4
Q

Describe action potential propagation

A

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

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5
Q

Why can the action potential only travel one way?

A

β†’ The sodium channels are plugged

β†’ Na+ can only move forwards

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6
Q

What are the 4 main neurotransmitters?

A

β†’ ACh
β†’ Glutamate
β†’ GABA
β†’ Glycine

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7
Q

What are amino acid neurotransmitters?

A

β†’ GABA
β†’ glutamate
β†’ glycine

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8
Q

Why are amino acid neurotransmitters called that?

A

β†’ their precursors are amino acids

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9
Q

How is glutamine turned into glutamate?

A

β†’ phosphate activated glutaminase

β†’ Amine group gets substituted by an oxygen

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10
Q

Where is glutamate synthesized?

A

β†’ In the nerve terminals

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11
Q

Describe how glutamate gets packaged into vesiscles

A

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

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12
Q

Where is the AMPA receptor found?

A

β†’ Post synaptically

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13
Q

What are the 3 ionotropic receptors for glutamate?

A

β†’ AMPA
β†’ NMDA
β†’ Kainate

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14
Q

Why do the ionotropic receptors for glutamate have those names?

A

β†’ They all have the endogenous agonist glutamate

β†’ They can be activated by exogenous compounds

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15
Q

What are the 4 subunit types of AMPA receptors?

A

β†’ GluA1
β†’ GluA2
β†’ GluA3
β†’GluA4

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16
Q

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

A

β†’ tqo GluA2 subunits
β†’ and two GluA1, 3 or 4
β†’ hetero-tetrameric

17
Q

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

A

β†’ 4 orthosteric binding sites

β†’ Two sites must be occupied for channel opening

18
Q

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

A

β†’ Current increases

19
Q

What protects against excitotoxicity in AMPA receptors?

A

β†’ Presence of GluA2 subunits prevent Ca2+ flow

20
Q

What are the 3 subunit types of NMDA receptors?

A

β†’ GluN1
β†’ GluN2
β†’ GluN3

21
Q

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

A

β†’ two GluN1 subunits
β†’ two GluN2 or GluN3
β†’ heterotetrameric

22
Q

What are the ligands for an NMDA receptor?

A

β†’ Glutamate
β†’ glycine
β†’ D-serine

23
Q

How do GluN3 subunits affect NMDA?

A

β†’ they are inhibitory

24
Q

What ion is important in synaptic plasticity?

A

β†’ Mg2+ block

25
Q

Describe the process of synaptic plasticity

A

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

26
Q

What are the 5 subunits of kainate receptors?

A 
β†’ GluR5
β†’ GluR6b
β†’ GluR7
β†’ KA1 
β†’ KA2
27
Q

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

A 
β†’ too much excitation 
β†’ damage to functioning of vesicular glutamate transporters
β†’ lots of glutamate in the cytosol
β†’ no gradient for transporters
β†’ glutamate is pumped out of the cell
β†’ released without stimulus
28
Q

What are the effects of excitotoxicity?

A 
β†’ mitochondrial damage
β†’ Oxidative stress
β†’ Apoptosis
β†’ Stroke
β†’ Autism & Alzheimers
29
Q

What type of receptors are metabotropic?

A

β†’ G couples receptors

30
Q

How many types of metabotropic receptor are there for glutamate?

A

β†’ 8 types

31
Q

What are the 3 subtypes of glutamate receptor?

A

β†’ 1 - MGlu1 and MGlu5
β†’ 2- MGlu2 and Mglu 3
β†’ 3 - MGlu 4, MGlu 6, MGlu 7, MGlu 8

32
Q

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

A

β†’ Gq

33
Q

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

A

β†’ Gi

34
Q

Where are the group 1 G protein subtype receptors found?

A

β†’ post synaptically

35
Q

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

A

β†’ Presynaptically

36
Q

What kind of a neurotransmitter is glutamate?

A

β†’ Excitatory

37
Q

What are the domains that make up a G protein?

A

β†’ Venus flytrap domain
β†’ 7 transmembrane domain
β†’cysteine rich domain
β†’ C terminus domain

38
Q

How can excitotoxicity be stopped?

A

β†’ memantine

β†’ a low affinity NMDA receptor

πš™πš‘πš’πšœπš’πš˜πš•πš˜πšπš’ 𝟸 : πš—πšŽπšžπš›πš˜πšœπšŒπš’πšŽπš—πšŒπšŽ (21 decks)

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