Neuropharmacology of GABAA and iGLU receptors

Question 1

What was the main point of prof Bowie showing the slide of the GABAR cartoon when he was in school?

Answer 1

To show that there isn’t one discrete binding site, but rather that drugs can bind anywhere on the receptor

Question 2

True/False? NMDARs, like AMPARs and KARs, have very few endogenous modulators

Answer 2

False

They have many, with different effects and sites

Question 3

What happens when Exon 5 is alternatively spliced out of GluN subunits?

Answer 3

They become more less sensitive to pH

Question 4

How does Alzheimer’s kill neurons and how does Memantine (try to) prevent this?

Answer 4

Extrasynaptic receptors signal for cell death (while synaptic receptors signal for cell survival)

Alzheimer’s patients tend to have excessive extrasynaptic signalling, and Memantine is supposed to prevent extrasynaptic signalling

Question 5

What is common to all putative roles of NMDARs in Alzheimer’s disease?

Answer 5

They all end in increased NMDAR activation

Question 6

Rank the three NMDAR subunit regions (NTD, LBD, TMD) in order of how likely a single aa change is to cause a functional mutation

Answer 6

NTD (lease likely)
LBD
TMD (most likely)

Question 7

How come so many drugs that affect GABA A receptors have such different effects?

Answer 7

They affect different subunits (which have different localizations in the brain)

Question 8

What are the two possible ligands that can bind GABAARs (generally speaking)? Where can they bind?

Answer 8

PAM and NAM

Extracellular region
Transmembrane helices
Pore region

Question 9

In which subunit does a single point mutation knockout a mouse’s response to BDZ?

Answer 9

Alpha 2

Question 10

What were the key findings of behavioural testing on mice?

Answer 10

Different alpha and beta subunit modifications can lead to different effects on a broad spectrum, and the same subunit in the brain can have a different effect on a subunit in the spinal cord