Receptors And Acetylcholine

Question 0

What are metabotropic receptors?

Answer 0

These a integral membrane proteins which have a 7 transmembrane domain and are linked to a G protein
Cause a slow response
Binds a neurotransmitter on its extracellular part
Activates signal cascades

Question 1

What are ionotropic receptors ?

Answer 1

Ligand gated ion channels
They have a binding site on the extracellular aspect for neurotransmitter to bind
Have a pore to allow the passage of ions- either depolarisation or hyperpolarisation
Involved in fast transmission

Question 2

If the membrane potential is at -90mV and you get an inward current of sodium ions what are deflection of the epsc and epsp ?

Answer 2

The epsc will have a downward deflection whilst the epsp will have an upward deflection

Question 3

If the membrane potential is at 0mV and sodium channels open what happens to the epsc and epsp?

Answer 3

Both the epsc and epsp remain flat because there is no net movement of ions

Question 4

If the membrane potential is at +70mV and the potassium channels are opened, what happens to the epsc and epsp ?

Answer 4

The epsc will have an upward deflection because potassium ions will be flowing out of the cell to cause an outward current to return membrane potential closer to its equilibrium potential
The epsp will be a downward deflection as the outward flow of current will cause the membrane potential to become more negative

Question 5

If the membrane potential was at - 70mV and chloride channels were opened, what would happen to the epsc and epsp ?

Answer 5

The epsc would be an upward deflection because chloride ions would be entering the cell
The epsp would be a downward deflection because chloride ions would be making the membrane potential ,ore negative

Question 6

What is temporal summation ?

Answer 6

It is combining of action potentials at the same synapse causing them to join together to elicit a larger post synaptic potential

Question 7

What is spatial summation ?

Answer 7

This is the combination of the different synapses on one post synaptic neurone and the effects caused on the psp

Question 8

What subunits are present in muscle nicotinic acetylcholine receptors ?

Answer 8

Alpha, beta, gamma, delta or epsilon

It is either delta or epsilon dependent upon the stage of development

Question 9

What subunits are present in nicotinic acetylcholine receptors in the brain ?

Answer 9

Alpha and beta

Question 10

How many alpha subunits have to be present in a nicotinic acetylcholine receptor and why ?

Answer 10

2

Because this is the subunit which binds acetylcholine and it binds 2 acetylcholine molecules

Question 11

How many transmembrane domains are present in a nicotinic acetylcholine subunit ?

Answer 11

4 and 1 always faces into the pore- (domain 2) this ones negatively charged amino acid helix is the filter which defines which ions are able to pass through the channel

Question 12

What are the 3 receptors for glutamate ?

Answer 12

NMDA
AMPA
Kainate

Question 13

What are NMDA receptors important for ?

Answer 13

Important in memory and learning

Question 14

Which glutamate receptors are the most important for excitation ?

Answer 14

AMPA

Question 15

What are kainate receptors thought to be involved in ?

Answer 15

Epilepsy

Question 16

Explain AMPA receptors ?

Answer 16

There are 2 types of AMPA receptors- one is made up of a GluR1 subunit and a GluR2 subunit while the other is made up of 2 GluR1 subunits
The r1 and r2 receptor is the most common and allows only the passage of sodium and potassium
The r1 recptir is produced as a consequence of activity or insult as it also allows the passage of calcium ions

Question 17

When are more GluR1 only glutamate receptors put into the membrane ?

Answer 17

When lots of synaptic activity is occurring

Because they allow the passage of calcium ions which cause a larger depolarisation and also can act as second messengers

Question 18

Explain the structure of NMDA receptors ?

Answer 18

They are tetramers made up of 2 NR1 subunits and 2 NR2 subunits
The nr1 is for binding glycine and the nr2 is for binding glutamate
Allow passage of sodium potassium and calcium
At rest they are blocked by magnesium

Question 19

When NMDA receptors become unblocked and allow flow of ions ?

Answer 19

If the AMPA receptors are open and cause depolarisation of the post synaptic neurone then there will no longer be a driving force for magnesium into the cell so it leaves the NMDA receptors
If another action potential occurs at the pre synaptic terminal then the NMDA receptors will still be unblocked so they will be able to allow the passage of ions and cause a larger excitation in the post synaptic neuron

Question 20

What is an antagonist of AMPA/kainate receptors ?

Answer 20

NBQX

Question 21

What is an antagonist of NMDA receptors ?

Answer 21

APV

Question 22

What type of receptor is a GABAa receptor ?

Answer 22

Ionotropic

Question 23

When are GABA receptors inhibitory and when are they excitatory ?

Answer 23

They are inhibitory when the neurone is mature- chloride ions enter the cell causing hyperpolarisation
they are excitatory when the neurone is immature- the chloride ions leave the cell causing depolarisation

Question 24

What are the steps the follow activation of a metabotropic receptor ?

Answer 24

The G protein is activated G protein subunits (alpha subunit and beta-gamma subunit) or intracellular messenger modulate ion channels Ion channels open Ions flow across the membrane

Question 25

What happens with noradrenaline binds to a beta-adrenergic receptor ?

Answer 25

``` Activates Gs protein Activate adenylate Cyclase Increases the amount of cAMP cAMP increases protein kinase A Protein kinase A increases protein phosphorylation ```

Question 26

What happens when glutamate binds to mGluR1 receptor ?

Answer 26

Activates Gq protein Activates phospholipase c This increase DAG and IP3 The DAG increase protein kinase C while the IP3 increase the release of calcium Protein kinase C increases protein phosphorylation and the increased calcium release activates calcium binding protein

Question 27

What happens when glutamate binds to mGluR2 receptors ?

Answer 27

``` Activates Gi protein Inhibits adenylate Cyclase Decreases cAMP This decrease protein kinase A Decrease protein phosphorylation ```

Question 28

What happens when dopamine binds to dopamine D2 receptor ?

Answer 28

``` Activates Gi protein Decreases adenylate Cyclase Decreases cAMP Decreases protein kinase A Decreases protein phosphorylation ```

Question 29

Which glutamate receptors are more dense on the postsynaptic membrane and which are more dense on the pre synaptic membrane ?

Answer 29

Group 1 more dense on postsynaptic | Group 2+3 more dense on presynaptic

Question 30

Why do metabotropic GABA receptors act as dimers ?

Answer 30

Made up of GABA R1 and R2 subunits- only the R1 binds GABA but it doesn't work on it own

Question 31

What is a heteroreceptor ?

Answer 31

Can inhibit the release of a neurotransmitter which is different from its own

Question 32

What is an auto receptor ?

Answer 32

If a receptor is present on both the presynaptic and post synaptic membrane the receptors on the presynaptic side are important in regulating the release of the neurotransmitter from that neuron

Question 33

How does mGluR2 act as an autoreceptor ?

Answer 33

Glutamate is released from presynaptic terminal It binds to mGluR2 on the presynaptic membrane Causes a reduction in adenylate Cyclase Reduction in cAMP This then affects ca channels Leading to a reduction in the release of neurotransmitter

Question 34

How is acetylcholine made ?

Answer 34

Made from acetyl CoA and choline using the enzyme choline acetyltransferase (ChAT)

Question 35

Why is ChAT enzyme so important ?

Answer 35

Because only cells which contain this enzyme will be able to produce acetylcholine

Question 36

How is the production of acetylcholine inhibited ?

Answer 36

It is inhibited by acetylcholine binding to an allosteric site on the ChAT enzyme

Question 37

What transporter is used to store acetylcholine ?

Answer 37

Stored into vesicles by vesicular acetylcholine transporter

Question 38

How is acetylcholine inactivated in the synaptic cleft ?

Answer 38

It is cleaved by acetylcholineesterase into acetic acid and choline Choline is recycled as we cannot make it in our bodies

Question 39

How does hemicolinium work ?

Answer 39

It reduces the signalling at cholinergic synapses because it blocks the reuptake of choline and therefore the subsequent formation of acetylcholine

Question 40

How does vesamicol work ?

Answer 40

It reduces signalling at cholinergic neurons by inhibiting acetylcholine uptake into vesicles for storage

Question 41

How does botulinium work ?

Answer 41

It reduces signalling at cholinergic neurons by blocking the snare proteins required for vesicle docking and release of the neurotransmitter

Question 42

How does nicotine work ?

Answer 42

It enhances signalling at cholinergic neurons because it is an agonist

Question 43

How does scopolamine work ?

Answer 43

It reduces signalling at cholinergic synapses by acting as a competitive antagonist to muscarinic acetylcholine receptors

Question 44

Where are the major clusters of cholinergic pathways in the CNS ?

Answer 44

Striatum - interneurons in caudate putamen and nucleus acumbens Basal forebrain - projections to the cortex and hippocampus Pontine tegmentum p- REM sleep

Question 45

How many muscarinic acetylcholine receptors are there and what are they coupled to ?

Answer 45

There are 5 The even ones are coupled to adenylate Cyclase The odd ones are coupled to phospholipase c

Question 46

Where is muscarinic ACh M1 expressed in the brain ?

Answer 46

In the cortex and hippocampus and striatum

Question 47

Where are muscarinic ACh M2 receptors expressed in the brain ?

Answer 47

More highly expressed in the heart but they are present throughout the brain - cortex and hippocampus

Question 48

Where are muscarinic ACh M3 receptors expressed in the brain ?

Answer 48

Cortex and hippocampus and hypothalamus

Question 49

Where are muscarinic ACh M4 receptors expressed in the brain ?

Answer 49

Forebrain, mostly striatum

Question 50

Where are muscarinic ACh M5 receptors expressed in the brain ?

Answer 50

In the midbrain dopamine neuron region