Brainscape's Knowledge GenomeTM

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


See full index

A PA20023 > GABA > Flashcards

GABA Flashcards

1
Q

What is GABA

A
  1. THE principal inhibitory transmitter in the CNS (>30% of brain synapses)
  2. Activates both ionotropic and metabotropic receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is GABA synthesised from

A
  1. Enzymatic synthesis from glucose via Kreb’s cycle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How is GABA inactivated

A
  1. Inactivated by reuptake by the GABA Transporters (GAT)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What can deficits in GABA transmission lead to

A
  1. Deficits in GABA transmission important in epilepsy and anxiety
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does glycine do

A
  1. Glycine also has a role as an inhibitory amino acid transmitter
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the synthesis of GABA

A
  1. Starts with glucose and via krebs cycle the product is alpha-ketoglutamate
  2. Then glutamate which is converted to GABA using glutamic acid decarboxylase GAD
  3. GABA is transported into vesicles by VGAT- vesicular transporter
  4. When membrane terminal depolarises calcium enters, vesicles fuse with membrane and GABA is released
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe how GABA is terminated

A
  1. Action is terminated when taken out of synapse by GABA transporters into astrocytes where it is metabolised
  2. Also taken up to nerve terminals where it is either taken up by synaptic vesicles or converted by GABA-transaminase into succinic semialdehyde
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the distribution of GABA

A
  1. 35% of neurones stain for Glutamic Acid Decarboxylase (GAD) – i.e. GABA neurones
  2. Not localized discretely
  3. GABA neurones play prominent role in cerebellum, basal ganglia, hippocampus, hypothalamus, cortex
  4. Principally in local interneurones- Connections limited to other neurones in local area
  5. Can be found in relay or projection neurones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is relationship with GABA and glutamate

A
  1. Balance each other out

2. GABA inhibits, glutamate excites

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

Describe GABA(A) receptor

A
  1. ligand gated ion channels
  2. permeable to Cl- ions
  3. primarily postsynaptic
  4. mediate fast (milliseconds) inhibition
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe GABA(B) receptor

A
  1. G-protein-coupled receptors (GPCR)
  2. coupled to Ca2+ and K+ ion channels
  3. pre and postsynaptic
  4. mediate slow inhibition (seconds-minutes)
  5. also inhibit transmitter release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe GABAC receptors (GABAA-rho (ρ) receptor)

A
  1. ligand gated Cl- channels
  2. postsynaptic mainly located in retina
  3. mediate fast (ms) inhibition
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the fast synaptic inhibition caused by GABA(A)

A
  1. Low intracellular Cl-
  2. GABA opens channel
  3. inward negative Cl- current
  4. Membrane hyperpolarizes
  5. Inhibitory postsynaptic potential (IPSP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the structure of GABA(A) receptor

A
  1. GABAA receptor subunits have 4 trans-membrane segments
  2. TM2 (one of 4 trans-membrane segments) is pore forming segment
  3. Functional receptors are pentameric combinations of different subunits arranged to form the integral ion channel
  4. Most prevalent receptor in mammalian brain consists of two α, two β and one γ-subunit
  5. GABA binds between α and β-subunits – so 2 molecules to activate receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe different GABAA structures

A
  1. Multiple isoforms of α, β and γ subunits
  2. Rarer subunits exist – δ, ε, π, θ and ρ
  3. Most prevalent receptor is α1/β2/γ2
  4. Different subunits confer distinct physiological properties
  5. Receptor pharmacology is subunit-dependent
  6. Inhibitory effect depends on composition.
  7. Differential spatial distribution of receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the binding sites of a GABA A receptor

A
  1. Benzodiazepine
  2. GABA
  3. barbiturate/anaesthetic binding site
  4. neurosteroid binding site
  5. channel blocking site
17
Q

Describe benzodiazepine binding site

A
  1. e.g. diazepam, lorazepam
  2. potentiate GABA
  3. increase frequency of channel opening
  4. anxiolytic (reduce anxiety), antidepressant, muscle relaxant
18
Q

Describe GABA binding site

A
  1. agonists: GABA, muscimol
  2. antagonists: bicuculline, gabazine
  3. At interface of alpha-beta subunits- 2 binding sites
19
Q

Describe barbiturate/anaesthetic binding site

A
  1. pentobarbital, thiopental, propofol
  2. potentiate GABA
  3. prolong open time of channel
  4. sedative, antiepileptic, anaesthetic
20
Q

Describe neurosteroid binding site

A
  1. derivatives of sex hormones
  2. increase or decrease
  3. endogenous GABA inhibition
  4. adjacent to barbiturate binding site
21
Q

Describe channel blocking site

A
  1. picrotoxin, pentylenetetrazole
  2. block Cl- permeability
  3. convulsant
22
Q

Describe action at GABAB receptors

A
  1. GABAB-receptors are Gαi/o coupled, 7-TM GPCRs
  2. Linked to K+-channels in postsynaptic neurones
  3. Linked to Ca2+-channels in presynaptic terminals
  4. Presynaptically- closes calcium channels to reduce transmitter release
  5. Postsynaptically- opens potassium channels eliciting a slow hyperpolarization
23
Q

What are the agonists and antagonists of GABAB recetpors

A
  1. Agonists: GABA, baclofen

2. Antagonists: 2-hydroxy- saclofen, CGP55845A

24
Q

Describe why functional GABAB receptors

are obligatory heterodimers

A
  1. Two GABAB-receptors GABABR1 + GABABR2
  2. R1 in endoplasmic reticulum
  3. R2 in cell membrane
  4. Neither is functional alone
  5. Dimerize via C-terminal to form functional GABABR
  6. R1 binds GABA not R2
25
Q

Describe the interactions of GABAA and GABAB receptors

A
  1. GABA can mediate fast and slow postsynaptic inhibition
  2. GABA can control its own release and strength of inhibition
  3. e.g. postsynaptic GABAA + presynaptic GABAB will lead to signal decreasing
26
Q

What are the therapeutic targets for GABAB receptors

A
  1. GABABR agonists (baclofen) for spasticity (muscle spasms, rigidity) in multiple sclerosis and related motor disorders
    - Activates postsynaptic GABABR on motor neurones
    - May also have sedative and anxiolytic effects
  2. GABABR antagonists for possible use in epilepsy
    - Blocks presynaptic GABABR on GABA neurones to prevent reduction of GABA release (can’t block Ca2+ channels now) and increase synaptic inhibition
    - May also be sedative

A PA20023 (19 decks)

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