GABA-A receptor electrophysiology

Question 1

Name the channels associated with epilepsy and migrains?

Answer 1

Sodium

potassium

calcium

GABAA

Nicotinic

Question 2

Name the channels associated with neuromuscular disorders?

Answer 2

Sodium

Potassium

Calcium

Chlorine

Nicotinic

Question 3

Name the channels associated with cerebellar ataxia and excessive startle?

Answer 3

Potassium

Calcium

Glycine

Question 4

Name the 5 ligands assocaited with Cys-loop receptors?

Answer 4

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

Question 5

Cys loop receptors characteristics?

Answer 5

Pentameric

Ligand-gated

Ion channel

Question 6

Name the two types of cysteine-loop receptors?

Answer 6

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

1.

Question 7

Normal consciousness?

Answer 7

A balance between excitatory and inhibitory influences.

Question 8

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

Answer 8

Glutamate and GABA

Question 9

Glutamate

Answer 9

Interact with the binding site with a lock and key effect

Allows sodium to travel down its gradient.

Question 10

GABA?

Answer 10

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

Allows chloride to travel down.

Question 11

Neuronal excitability

Answer 11

The summation of multiple excitatory inputs initiates an AP.

Inhibitory synpases can prevent the excitatory event.

aS13

Question 12

What happens during seizures?

Answer 12

EEG: high amplitude during seizure.

Much larger in amplitude and must more less sychronised.

Post midazolam: stimulates GABA system- stop a seizure

Question 13

Sedations used to control seizures?

Answer 13

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.

Question 14

GABA_A receptor?

Answer 14

Allosteric binding site: GABA.

Steroids: endogenous.

Inverse antagonist is bicuculine and gabazine.

Question 15

Propofol?

Answer 15

Binds to the barbiturate site of the GABAA receptor.

Question 16

Patch clamp recording?

Answer 16

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.

Question 17

What receptors does propofol modulates?

Answer 17

GABAA

Glycine receptors

Question 18

What does GABAA receptor look like?

Answer 18

5 domains

7TM domains

Question 19

GABAA receptor activation?

Answer 19

3 state model.

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

Question 20

Extrasynaptic GABAA receptors?

Answer 20

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.

Question 21

Tonic current

Answer 21

producing and restoring normal current.

Question 22

What GABA receptors are responsible for the extrasynpatic tonic current?

Answer 22

alpha4 and alpha 6

Question 23

How is there so many different types of epilepsy?

Answer 23

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

Question 24

BIC?

Answer 24

Non-competitive

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

Question 25

PIC?

Answer 25

Can cause seizures.

Question 26

What does BIC do?

Answer 26

It inhibits small tonic current. Can be reversed by GBZ. Suggesting BIC binds to the GABA site.

Question 27

What 3 things can cause epilepsy?

Answer 27

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

Question 28

GBZ activity?

Answer 28

Reverses the tonic current.

Question 29

Structural model on how GABA binds to the receptor

Answer 29

AS16

Question 30

structural models of pentameric ligand-gated ion channels?

Answer 30

Crystallisation is not able to occur when the loop is present

Question 31

Homoer receptors?

Answer 31

2 subunit receptor Ligand gated. Wont bind GABA properly.

Question 32

Mutation in alpha1 subunit associated with?

Answer 32

Autosomal dominant juvenile myoclonic epilepsy ADJME

Question 33

Mutation in the gamma2 subunit associated with?

Answer 33

Childhood absence epielspy (CAE) Febrile seizures (FS) Generalised Epilepsy with febrile seizures (GEFS)

Question 34

Delta subunit mutation is associated with?

Answer 34

Generalised epilepsy with febrile seizures plus GEFS

Question 35

Mutation in the GABA-activated ion channel?

Answer 35

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

Question 36

Where does the lys residue lie in the GABA receptor?

Answer 36

In the TM2 and tm3

Question 37

What is neccesary for gating?

Answer 37

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.

Question 38

What happens if you mutate the alpha subunit?

Answer 38

Change in the type of activity Short duration of openings

Question 39

What happens when the gamma subunit mutates?

Answer 39

Reduction in the amount of time the channel stays opened