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E: Neuropsychopharmacology > GABA-A receptor electrophysiology > Flashcards

GABA-A receptor electrophysiology Flashcards

1
Q

Name the channels associated with epilepsy and migrains?

A

Sodium

potassium

calcium

GABAA

Nicotinic

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2
Q

Name the channels associated with neuromuscular disorders?

A

Sodium

Potassium

Calcium

Chlorine

Nicotinic

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3
Q

Name the channels associated with cerebellar ataxia and excessive startle?

A

Potassium

Calcium

Glycine

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4
Q

Name the 5 ligands assocaited with Cys-loop receptors?

A
  1. ACh
  2. 5-HT (serotonin)
  3. Zn
  4. GABA
  5. Glycine
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5
Q

Cys loop receptors characteristics?

A

Pentameric

Ligand-gated

Ion channel

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6
Q

Name the two types of cysteine-loop receptors?

A
  1. Cation (positively charged ion)
  2. Anion (negatively charged ion)

1.

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7
Q

Normal consciousness?

A

A balance between excitatory and inhibitory influences.

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8
Q

Name the two types of neurotransmitters that are important for the brain?

A

Glutamate and GABA

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9
Q

Glutamate

A

Interact with the binding site with a lock and key effect

Allows sodium to travel down its gradient.

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10
Q

GABA?

A

Interacts with their binding site with a lock and key effect.

Allows chloride to travel down.

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11
Q

Neuronal excitability

A

The summation of multiple excitatory inputs initiates an AP.

Inhibitory synpases can prevent the excitatory event.

aS13

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12
Q

What happens during seizures?

A

EEG: high amplitude during seizure.

Much larger in amplitude and must more less sychronised.

Post midazolam: stimulates GABA system- stop a seizure

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13
Q

Sedations used to control seizures?

A

Midazolam: induces a state similar to sleep.

Propofol: flat line the EEG. Abolises all brain function. Genereal anestertic.

General anaesteritics are powerful and can enhance GABA effects and synthesis.

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14
Q

GABAA receptor?

A

Allosteric binding site: GABA.

Steroids: endogenous.

Inverse antagonist is bicuculine and gabazine.

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15
Q

Propofol?

A

Binds to the barbiturate site of the GABAA receptor.

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16
Q

Patch clamp recording?

A

AS14

Technique used to determine the function of channels (those within the patch clamp).

Inside out: good as you change the electrical activity.

Outside out: best to look at neurotransmitter activity. Can record the electrical activity.

17
Q

What receptors does propofol modulates?

A

GABAA

Glycine receptors

18
Q

What does GABAA receptor look like?

A

5 domains

7TM domains

19
Q

GABAA receptor activation?

A

3 state model.

Receptor exist in the unbound state: bound to agonist state and the activation state (only if agonist is potent enough)

20
Q

Extrasynaptic GABAA receptors?

A

AS15

GABAA receptors are found a number of different locations.

Extrasynpatic receptors give rise to a tonic current. When there is a lot of electrical activity, spill over of GABA reaches the extrasynaptic receptor.

21
Q

Tonic current

A

producing and restoring normal current.

22
Q

What GABA receptors are responsible for the extrasynpatic tonic current?

A

alpha4 and alpha 6

23
Q

How is there so many different types of epilepsy?

A

As mutations in any of these receptors can affect phasic or tonic current.

24
Q

BIC?

A

Non-competitive

Binds from the inside of the cell and plugs the channel.

25
Q

PIC?

A

Can cause seizures.

26
Q

What does BIC do?

A

It inhibits small tonic current.

Can be reversed by GBZ.

Suggesting BIC binds to the GABA site.

27
Q

What 3 things can cause epilepsy?

A
  1. Affecting the phasic current
  2. Tonic current spontaneous opening
  3. Tonic current by GABA agonist
28
Q

GBZ activity?

A

Reverses the tonic current.

29
Q

Structural model on how GABA binds to the receptor

A

AS16

30
Q

structural models of pentameric ligand-gated ion channels?

A

Crystallisation is not able to occur when the loop is present

31
Q

Homoer receptors?

A

2 subunit receptor

Ligand gated.

Wont bind GABA properly.

32
Q

Mutation in alpha1 subunit associated with?

A

Autosomal dominant juvenile myoclonic epilepsy

ADJME

33
Q

Mutation in the gamma2 subunit associated with?

A

Childhood absence epielspy (CAE)

Febrile seizures (FS)

Generalised Epilepsy with febrile seizures (GEFS)

34
Q

Delta subunit mutation is associated with?

A

Generalised epilepsy with febrile seizures plus

GEFS

35
Q

Mutation in the GABA-activated ion channel?

A

Show sign of seizure

Depends on where the mutation is and what does it affect such as structure or function

36
Q

Where does the lys residue lie in the GABA receptor?

A

In the TM2 and tm3

37
Q

What is neccesary for gating?

A

The position of the positively charged amino acids.

Need to keep the space fill of the loop- so the b1/b2 loop can fit in it.

38
Q

What happens if you mutate the alpha subunit?

A

Change in the type of activity

Short duration of openings

39
Q

What happens when the gamma subunit mutates?

A

Reduction in the amount of time the channel stays opened

E: Neuropsychopharmacology (9 decks)

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