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LF261: Neuropharmacology > Lecture 10. Glutamatergic Synaptic Transmission and the Trafficking of Transmembrane Receptors > Flashcards

Lecture 10. Glutamatergic Synaptic Transmission and the Trafficking of Transmembrane Receptors Flashcards

1
Q

What is the major excitatory neurotransmitter in the mammalian CNS?

A

L-Glutamate

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2
Q

What are L-glutamate ligand-gated ion channels called?

A

Ionotropic GluRs (iGluR)

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3
Q

What are L-glutamate G-protein coupled receptors called?

A

Metabotropic GluRs (mGluR)

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4
Q

What are the three types of iGluRs?

A

NMDA receptor
AMPA receptor
Kainate receptor

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5
Q

What G-protein are coupled to group I mGluRs?

A

Gαq

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6
Q

What G-protein are coupled to group II mGluRs?

A

Gαi

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7
Q

What G-protein are coupled to group III mGluRs?

A

Gαi

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8
Q

What is the obligatory receptor of NMDA?

A

GluN1 (has to be there or else not a NMDA receptor)

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9
Q

What are the three subunits of NMDA receptors?

A

GluN1
GluN2A-D
GluN3A,B

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10
Q

What are the four subunits of AMPA receptors?

A

GluA1-4

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11
Q

What are the five subunits of kainate receptors?

A

GluK1-5

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12
Q

What are the two subtypes of mGluR group I?

A

mGlu1
mGlu5

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13
Q

What are the two subtypes of mGluR group II?

A

mGlu2
mGlu3

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14
Q

What are the four subtypes of mGluR group III?

A

mGlu4
mGlu6
mGlu7
mGlu8

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15
Q

What effect are brought about by iGluRs?

A

Fast, excitatory

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16
Q

What effect are brought about by mGluRs?

A

Slow, excitatory or inhibitory

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17
Q

How does glutamate arise in the synapse?

A

Either converted from glutamine taken up by the neurone from a glial cell/astrocyte or as a product of the tricarboxylic acid cycle

18
Q

How is glutamate packed into vesicles?

A

Through the creation of a H⁺ ion gradient that supports the uptake of Glu⁻

19
Q

What uptakes glutamate, allowing glutamate supply to be recycled?

A

EAAT1-4 (excitatory amino acid transporter)

20
Q

What EAATs are located on the glial cell?

A

EAAT1-2

21
Q

What EAATs are located on the neurone?

A

EAAT3-4

22
Q

Why do glial cells possess EAAT?

A

Due to being in close proximity of the neurone (tripartite synapse)

23
Q

How many agonists must bind to the NMDA receptor to activate it?

A

2

24
Q

What ion blocks the transmembrane pore?

A

Mg²⁺

25
Q

What are the co-agonists of the NMDA receptor that bind to GluN1?

A

Glycine and D-serine (normally always present so don’t think about them)

26
Q

What ion regulatory site is present on GluN2?

A

Zn²⁺

27
Q

What does rectifying mean?

A

When the flow of ions through a channel is favoured in one direction supposed to the other direction

28
Q

What can AMPA receptor subunits affect?

A

Function, can fine tune activity due to certain stimuli. Can cause post-translational modifications that can influence the function of particular circuits

29
Q

What does arginine block?

A

Ca²⁺

30
Q

What is the difference in I/V curve between Ca²⁺-permeable and Ca²⁺-impermeable AMPA receptors?

A

Ca²⁺-permeable = rectifying
Ca²⁺ impermeable = linear

31
Q

What are the roles of glutamate receptors in the mammalian brain?

A

Mediate the majority of fast excitatory synaptic transmission in the CNS
Vital to many basic functions – cognition, movement, central cardiovascular, thermoregulatory & respiratory control
Changes in glutamatergic synaptic strength may underpin learning and memory
Implicated in a host of neurodevelopmental, neurological, neurodegenerative and psychiatric conditions (eg autism, epilepsy, stroke, Alzheimer’s disease, schizophrenia)
Target of drugs of abuse – Ketamine (Special K), Phencyclidine (PCP; Angel Dust)

32
Q

What are the trafficking levels into and out of synapses?

A

Very high

33
Q

Why does Mg²⁺ block NMDA receptors when the cell is hyperpolarised?

A

The ion is more strongly attracted to the receptor, ion attracted more strongly into the channel

34
Q

What are active synapses?

A

Transmits information at hyperpolarised (resting) membrane potentials through AMPA receptors

35
Q

What are silent synapses?

A

Ones that lacks AMPARs at the synapse and does NOT transmit information at hyperpolarised (resting) membrane potentials due to the Mg²⁺ block of the NMDA receptor. AMPA receptors may be stored in intracellular vesicles or at extrasynaptic sites

36
Q

Synapses containing NMDAR can recruit what?

A

AMPAR through pairing protocol (creates response at -65mV)

37
Q

How can the movement of AMPARS to the synaptic cleft be visualised?

A

Through the use of a latex bead or staining with a quantum dot

38
Q

What is long-term potentiation?

A

When high plasticity is induced in the brain thorough high frequency stimulation

39
Q

What is long-term depression?

A

When low plasticity is induced in the brain thorough low frequency stimulation, decreasing the size of the response

40
Q

What are NMDARs necessary for?

A

Long-term potentiation and spatial learning

41
Q

What are the implications of AMPAR trafficking at synapses?

A

Trafficking may underlie learning and memory, as well as a host of pathological and psychiatric conditions
This clinical relevance encourages the synthesis of subtype/subunit selective GluR-based drugs and hopes for new treatments

LF261: Neuropharmacology (15 decks)

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