AMPARs and NMDAR Diversity Flashcards

1
Q

Which is faster, NMDARs or AMPARs?

A

AMPARs, by a lot

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2
Q

What is a property of all AMPARs (that is not subunit dependent)?

A

High Open probability and rapid activation

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3
Q

What is a property of AMPARs that IS Subunit dependent?

A

Desensitization recovery (how long it takes before a stimulus depolarizes the channel, different cases for sound or light)

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4
Q

Describe the shared architecture of AMPARs and NMDARs in terms of their domains, polymerity, and shape

A

Amino Terminal Domain
Ligand Binding Domain
TransMembrane Domain

Homo or heterotetramers with different subgroups that alter pharmacology (two sets of 2 subunits)
Crossing over of 2 proteins between ATD and LBD

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5
Q

What is unique about the GluA2 AMPA Receptor subunit?

A

They are edited at the Q/R/N site of the M2 loop

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6
Q

Where is the Q/R/N site located in the assembled protein and what is the function?

A

At the apex of the pore, allows the pore to open/close by twisting open (on a matter of angstroms)

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7
Q

What did Prof Bowie notice about when depolarizing a cell?

A

Ohm’s law (P = IR) did not apply

meaning something must be offsetting the rectification

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8
Q

What is a property of polyamines?

A

They can restore rectification

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9
Q

What is the only AMPAR subunit that does not have rectification?

A

GluA2

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10
Q

How do polyamines block AMPARs?

A

The Q/R/N site creates a block site that is electronegative, big clunky polyamine hesitates inside and gets stuck

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11
Q

AMPARs preferentially form what type of polymer? What form is favored and which are unstable?

A

Heteromers

Some homomers are permitted but mostly 2:2 stoichiometry is favored

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12
Q

What are the auxiliary subunits mentioned in class and what do they do?

A

TARP, Cornichons, CKAMP44, SynDIG1, GSG1L

They bind to AMPA receptors and modify functions

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13
Q

What is an advantage of the heavy regulation of AMPARs?

A

Different regions of the brain have specific regulation, allowing for drug specificity

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14
Q

What is the role of TARP?

A

Bus that transports AMPARs to the synapse

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15
Q

How do TARPs and CNIHs regular AMPAR gating behaviour?

A

Increasing the signalling time through the KGK site of GluA2

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16
Q

What is common for nascent AMPAR RNA?

A

Alternate splicing and RNA editing

17
Q

What are the two functional AMPAR families?

A

GluA2-containing, and -lacking

18
Q

What are the 3 properties of GluA2-containing AMPARs?

A

They are Ca2+ impermeable, polyamine-insensitive, and have low unitary conductance

19
Q

What are the 3 properties of GluA2-lacking AMPARs?

A

They are Ca2+ permeable, polyamine-sensitive, and have high unitary conductance

20
Q

True/False? There are many mechanisms designed to relieve AMPAR polyamine block

A

True

21
Q

What are the two most important features of NMDA receptors?

A

High Ca permeability (useful for brain plasticity and maturation)

Gating properties (Mg blocks the pore until it is depolarized, then lets Ca in)

22
Q

Define the slow gating found in NMDA receptors

A

A single ms pulse of glutamate will keep the channel open for hundreds of milliseconds

23
Q

Define the polymerity of NMDA receptors

A

Obligate tetramers
GluN1, binds glycine
GluN2, binds glutamate
(GluN3 not talked about but binds glycine)

24
Q

Which NMDA subunit has different types? What is the difference between them?

A

GluN2 (has 4)
GluN3 (has 2)

Different types of subunit have different pharmacologies

25
Q

Which heteromer of DNMAR is relatively the fastest to open? Why “relatively”?

A

GluN1-GluN2A

Relatively because it’s on the order of 100 ms compared to the ~5 ms of an AMPAR

26
Q

Which heteromer of DMNAR is the slowest to open?

A

GluN1-GluN2D

opens for ~10s

27
Q

Which NMDA subunit has the highest Single-Channel conductance? The lowest?

A

HIghest: 2A and 2B (tied)
Lowest: 2C and 2D (tied)

28
Q

Which NMDA subunit has the highest open probability? the lowest?

A

Highest: 2A
Lowest: 2C and 2D (tied)

29
Q

Why are NMDARs considered “coincidence detectors”?

A

Only open when the cell is depolarized (relies on Mg2+ block)

30
Q

Which GluN2 type has an expression profile that overlaps with GluN1?

A

GluN2A-D

31
Q

How are NMDARs regulated?

A

Numerous endogenous modulators