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Neurobiology > Receptors And Acetylcholine > Flashcards

Receptors And Acetylcholine Flashcards

0
Q

What are metabotropic receptors?

A

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

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1
Q

What are ionotropic receptors ?

A

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

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2
Q

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

A

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

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3
Q

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

A

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

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4
Q

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

A

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

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5
Q

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

A

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

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6
Q

What is temporal summation ?

A

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

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7
Q

What is spatial summation ?

A

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

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8
Q

What subunits are present in muscle nicotinic acetylcholine receptors ?

A

Alpha, beta, gamma, delta or epsilon

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

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9
Q

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

A

Alpha and beta

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10
Q

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

A

2

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

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11
Q

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

A

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

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12
Q

What are the 3 receptors for glutamate ?

A

NMDA
AMPA
Kainate

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13
Q

What are NMDA receptors important for ?

A

Important in memory and learning

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14
Q

Which glutamate receptors are the most important for excitation ?

A

AMPA

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15
Q

What are kainate receptors thought to be involved in ?

A

Epilepsy

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16
Q

Explain AMPA receptors ?

A

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

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17
Q

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

A

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

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18
Q

Explain the structure of NMDA receptors ?

A

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

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19
Q

When NMDA receptors become unblocked and allow flow of ions ?

A

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

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20
Q

What is an antagonist of AMPA/kainate receptors ?

A

NBQX

21
Q

What is an antagonist of NMDA receptors ?

A

APV

22
Q

What type of receptor is a GABAa receptor ?

A

Ionotropic

23
Q

When are GABA receptors inhibitory and when are they excitatory ?

A

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

24
Q

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

A

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

25
Q

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

A 
Activates Gs protein
Activate adenylate Cyclase
Increases the amount of cAMP
cAMP increases protein kinase A
Protein kinase A increases protein phosphorylation
26
Q

What happens when glutamate binds to mGluR1 receptor ?

A

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

27
Q

What happens when glutamate binds to mGluR2 receptors ?

A 
Activates Gi protein 
Inhibits adenylate Cyclase 
Decreases cAMP 
This decrease protein kinase A 
Decrease protein phosphorylation
28
Q

What happens when dopamine binds to dopamine D2 receptor ?

A 
Activates Gi protein 
Decreases adenylate Cyclase 
Decreases cAMP 
Decreases protein kinase A 
Decreases protein phosphorylation
29
Q

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

A

Group 1 more dense on postsynaptic

Group 2+3 more dense on presynaptic

30
Q

Why do metabotropic GABA receptors act as dimers ?

A

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

31
Q

What is a heteroreceptor ?

A

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

32
Q

What is an auto receptor ?

A

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

33
Q

How does mGluR2 act as an autoreceptor ?

A

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

34
Q

How is acetylcholine made ?

A

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

35
Q

Why is ChAT enzyme so important ?

A

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

36
Q

How is the production of acetylcholine inhibited ?

A

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

37
Q

What transporter is used to store acetylcholine ?

A

Stored into vesicles by vesicular acetylcholine transporter

38
Q

How is acetylcholine inactivated in the synaptic cleft ?

A

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

39
Q

How does hemicolinium work ?

A

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

40
Q

How does vesamicol work ?

A

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

41
Q

How does botulinium work ?

A

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

42
Q

How does nicotine work ?

A

It enhances signalling at cholinergic neurons because it is an agonist

43
Q

How does scopolamine work ?

A

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

44
Q

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

A

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

45
Q

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

A

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

46
Q

Where is muscarinic ACh M1 expressed in the brain ?

A

In the cortex and hippocampus and striatum

47
Q

Where are muscarinic ACh M2 receptors expressed in the brain ?

A

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

48
Q

Where are muscarinic ACh M3 receptors expressed in the brain ?

A

Cortex and hippocampus and hypothalamus

49
Q

Where are muscarinic ACh M4 receptors expressed in the brain ?

A

Forebrain, mostly striatum

50
Q

Where are muscarinic ACh M5 receptors expressed in the brain ?

A

In the midbrain dopamine neuron region

Neurobiology (30 decks)

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