Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neuropharmacology > GABA 1 > Flashcards

GABA 1 Flashcards

1
Q

Who first discovered GABA?

A

Roberts and Frankel in 1950

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How was GABA discovered?

A

Paper chromatography of brain extracts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Florey 1953

A

Showed that brain extracts have inhibitory action on crayfish stretch receptor organ

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Kuffler 1958

A

Applied GABA mimicked inhibitory action on crayfish stretch receptor organ

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Roberts: 1950s and 60s

A

Elucidated GABA metabolism through radioactive precursors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Obata 1967

A

Iontophoretic gather application mimics inhibitory action of Purkinje cells and released into ventricles on Purkinje stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

GABA levels in the brain

A

2500 nmol/gram

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Is there more inhibition or excitation in the brain?

A

Inhibition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How is GABA distributed?

A

Throughout the brain (30% of all nerve endings)
inhibitory interneurons everywhere
long axon tracts: cortex-substantia nigra; cerebellar Purkinje cells (and many others)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How was the distribution of GABA determined?

A

Distribution of GABA receptors (Promoter:fusion/mRNA/Protein) Distribution of metabolising enzymes (GAD, GABA-T) Distribution of GABA and/or vesicular GABA transporter Uptake of 3H GABA Electrophysiology (gold standard)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Recurrent inhibition

A

Draw diagram

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Afferent inhibition

A

Draw diagram

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

The GABA shunt

A

draw diagram

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

GABA transaminase (GABA-T)

A

Catalyses the conversion of Alpha-ketoglutarate to glutamate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Glutamic acid decarboxylase (GAD)

A

Catalyses the conversion of glutamate to GABA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Vesicular transport of GABA

A

VGAT

17
Q

Reuptake

A

2Na+/1Cl- per GABA 4 Distinct Genes:GAT-1,2,3 & BGT-3 ( GABA/betaine transporter) Nerve Terminals and Glial membranes

18
Q

Which of the GABA transporters have established blockers?

A

GAT etc…

VGAT doesn’t

19
Q

Coupling of synthesis and transport

A

Draw diagram

20
Q

What is GABA synthesis coupled to?

A

GABA synthesis is functionally coupled to vesicular transport into synaptic vesicles

21
Q

How many variants of GAD are there in humans?

A

There are two variants: 65 and 67

22
Q

Why is GABA synthesized by SV-associated GAD is preferentially transported into the SV by vesicular GABA transporters (VGATs)?

A

VGAT forms a protein complex with GAD on the SV

23
Q

Succinic semialdehyde dehydrogenase deficiency

A

First documented inborn error of GABA metabolism

symptoms include mental retardation, ataxia, motor deficiencies

24
Q

Disorders related to aberrant GABA transmission

A

Epilepsy, Huntington’s disease, Parkinson’s disease, tardive dyskinesia, alcoholism, sleep disorders

25
Q

Physiology of GABAergic transmission

A

Draw diagram

26
Q

When is GABA transmission excitatory?

A

In invertebrates and developing neurons

27
Q

GABAergic transmission in. embryonic neurons

A

Draw diagram

28
Q

GABAergic transmission in some adult neurons

A

Draw a diagram

29
Q

GABA receptors

A

Historically there were three classes but now there are technically two, as C is now a subtype of A

30
Q

GABAA, and GABAC

A

Classic Ligand-gated ion channels analogous to nicotinic receptor - postsynaptic

31
Q

GABAB

A

7TM G-Coupled receptors – presynaptic (coupled to K+ channels)

32
Q

Identification of the GABA receptors

A

Hans Mohler – 1980’s
Photolabelling
Eric Barnard & Anne Stephenson – 1980’s
Purified and reconstituted protein
Eric Barnard’s & Peter Seeburg’s groups – 1986-7
Sequenced via cDNA based on peptides

33
Q

Compare GABAA and GABAC receptors

A

Draw the table

34
Q

GABAA receptors

A

19 different subunits α1-6, β1-4, γ1-3,δ,ε,θ
8 families alternative splicing exists
most common form: α12,β22,γ21

35
Q

Mechanism of activation

A

Two agonist molecules needed to open channel
Agonist binding is very rapid, low affinity (Kd 100 µmol)
rapid confirmation change opens channel (milliseconds)
Desensitisation involves transition to high affinity state (Kd > 1 µmol)

36
Q

Which proteins are GABAA receptors usually clustered with?

A

GABARAP
Neuroligin-2
Gephyrin
Collybistin

37
Q

How does clustering affect GABAA receptor kinetics?

A

Clustering decreases affinity and decreases the rate of desensitisation
Clusters have properties consistent with those of native synaptic transmission

38
Q

Extrasynaptic GABAA receptors

A

Lower EC50 thus more sensitive

39
Q

Tonic inhibition in clustered and diffuse GABAA receptors

A

Draw diagrams

IPSP in clustered but not diffuse

Neuropharmacology (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions