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NSB Lectures > Chemistry & Physiology of the Synapse > Flashcards

Chemistry & Physiology of the Synapse Flashcards

1
Q

What are the two types of receptor on post-synaptic membranes?

A

Ligand-gated (Ionotropic)
G-Protein Coupled (Metabotropic)

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2
Q

Which is the receptor that has the fastest response - and why?

A

Ligand-gated (inotropic) - because the ligand binds, shape changes and ions can immediately flow through - the least amount of things needed to do for an effect to take place. There is an immediate response.

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3
Q

What are ionotropic receptors activated by?

A

The binding of a ligand.

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4
Q

How do ionotropic receptors work?

A

A ligand binds to the transmitter binding site extracellularly on one of the subunits of the receptor. This causes the transmembrane domain to change shape (conformational change). This allows the channel pore to open and for certain ions to flow freely through it, across the membrane and become intracellular.

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5
Q

What is ion permeability of a receptor?

A

The degree to which ions are permitted to cross the central pore.

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6
Q

What is ion conductance?

A

How many ions can cross the pore in a certain amount of time.

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7
Q

What are the dynamics and kinetics of a receptor?

A

How well a NT binds to the receptor, how fast the receptor undergoes conformational change and how long it lasts for.

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8
Q

What is ligand affinity of a receptor?

A

The affinity of which a NT can bind to the receptor.

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9
Q

What is a drug called that binds to the receptor and induces a response?

A

Agonist

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10
Q

What is a drug called that inhibits the binding of a NT or agonist to the receptor?

A

Antagonist

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11
Q

Can a receptor be activated by a single type of NTs or can it be activated by multiple types?

A

It depends on the receptor - most can be activated by different NTs (multiple site binding) but some are single-site binding.

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12
Q

What is a multiple site binding receptor?

A

An ionotropic receptor that can be activated by more than one NT.

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13
Q

Name three types of ionotropic receptors that respond to Glutamate (NT).

A

AMPA
NMDA
Kainate

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14
Q

How many subunits is the Glutamate AMPA receptor made from (and what are they?)

A

4 subunits -
GluA1
GluA2 x2
GluA3

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15
Q

Which ion does the GluA2 subunit primarily allow to cross the membrane?

A

Na+

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16
Q

Which receptor is found in 90% of brain synapses?

A

Glutamate AMPA

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17
Q

What impact does having different combinations of subunits have upon receptors?

A

It allows different rates of conformational change - therefore it impacts on the speed at which an effect is observed between different receptors.

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18
Q

What type of response is generated by a receptor that allows the movement of Na+ ions (e.g. GluA2) - excitatory or inhibitory?

A

Excitatory - Na+ ion movement results in depolarisation

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19
Q

Is depolarisation excitatory or inhibitory?

A

Excitatory

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20
Q

If one receptor opens and allows movement of Na+ ions across the membrane, is it guaranteed that an AP will result?

A

No - you MUST meet the threshold required for generation of an AP = requires activation of many channels, not just one.

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21
Q

How many subunits is the Glutamate NMDA receptor (GluR NMDA) made from and what are they?

A

2 - GluN1 & GluN2

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22
Q

Which agonists need to bind to GluR NMDA in order for it to be activated?

A

Glutamate and glycine - both need to bind for activation.

23
Q

GluR NMDA has a glycine and a glutamate bound - does this mean that the channel will immediately open?

A

No - GluR NMDA needs repeated depolarisations to open the channel - this is due to the inhibitory Mg2+ ion.

24
Q

How does a Mg ion control the opening of the GluR NMDA receptor?

A

Mg is strongly positive (2+) and therefore has a strong attraction to the negative intracellular space. This holds the receptor in the closed position.

As repeated depolarisations occur, the intracellular space becomes more positive, weakening the attraction of the Mg ion and allowing it to undergo conformational change and open the channel.

25
Q

Which ion moves through the GluR NMDA when it is open?

A

Calcium (Ca2+)

26
Q

Is GluR NMDA a fast or slow receptor?

A

It is ionotropic so it is fast HOWEVER it is slower compared to GluR AMPA.

27
Q

When the GluR NMDA opens and Calcium ions flow in - what does this do?

A

Calcium entering initiates a biochemical cascade of reactions.

28
Q

How does GluR NMDA protect against ischaemic acidosis?

A

The outer domain of the receptor is pH sensitive - if the extracellular environment is acidic the receptor opens less frequently.

29
Q

Name 2 things it is thought that GluR NMDA are involved in in the brain.

A

Formation of long term memory (possibly)

Neuroplasticity

30
Q

Name 4 different ionotropic receptors.

A

Glutamate AMPA
Glutamate NDMA
GABA
Acetylcholine

31
Q

Is a GABA receptor excitatory or inhibitory?

A

Inhibitory (depressive)

32
Q

Why GABA opens, which ion flows?

What effect does this have on the voltage of the cell?

How does this affect APs?

A

Cl- flows in.

Causes hyperpolarisation - makes the cell more negative.

Inhibits the neuron from firing an AP.

33
Q

How can GABA receptor stimulation be overcome?

A

By increasing the amount of glutamate - is a balancing act between glutamate and GABA levels as to which response you get.

34
Q

Where are AChR found?

A

At the neuromuscular junction

35
Q

How many subunits are there in an AChR?

A

Five subunits - 2 x ⍺, β, 𝛾 & 𝛅.

36
Q

How many molecules of ACh bind to AChR (and at which part?).

A

2 x molecules of ACh bind - one to each of the ⍺ units.

37
Q

What is the firing of a post-synaptic neuron dependant upon?

A

The integration of all signals that it receives - both excitatory and inhibitory.

38
Q

What is -
- GluR
- GluRm

A

Glutamate ionotropic receptor

Glutamate metabotropic receptor

39
Q

What is synaptic integration?

A

The process of adding (summation) all the signals received together before generating an AP.

Therefore - adding all the positives and negatives to determine whether the threshold is reached to fire an AP.

40
Q

What is dendritic integration?

A

Same thing as synaptic integration - it just occurs on the dendrites rather than at a synapse.

41
Q

What is summation of signals?

A

Adding different signals together (positive and/or negative)

42
Q

What is the post-synaptic potential (i.e. excitatory or inhibitory) of the following NTs:

GABA
Glutamate
Glycine
Nicotinic
Serotonin
ATP

A

GABA - inhibitory (brain)

Glutamate - excitatory

Glycine - inhibitory (spinal cord and brain stem)

Nicotinic - excitatory (NMJ) and excitatory/modulatory (CNS)

Serotonin - excitatory or modulatory

ATP - excitatory

43
Q

How do G-protein receptors work?

A

The ligand (NT) binds to the outside of the receptor - causes a conformational change on the intracellular side of the receptor.

This causes G protein (made of GDP + ⍺, β & δ) to split - β & δ bind to the receptor, ⍺ & GTP (changed) - moves away and interacts with various bits in the cells (e.g. other receptors, enzymes, proteins) causing biochemical cascade.

44
Q

In a G-protein receptor, what is the middle part that crosses the membrane called?

A

Transmembrane helixes - usually around 7 of them within the membrane.

45
Q

What happens when a Gs protein receptor is activated?

A

Stimulation

Inc AC - inc cAMP - inc PKA - inc protein phosphorylation

46
Q

What happens when a Gi protein receptor is activated?

A

Inhibition

Dec AC - dec cAMP - dec PKA - dec phosphorylation

47
Q

What happens with a Gq protein receptor is activated?

A

Inc PLC
- Inc DAG inc PKC
- Inc IP3 and in Ca
Inc phosphorylation

48
Q

Name an NT that stimulates Gs protein receptors.

A

Noradrenaline

49
Q

Name an NT that stimulates Gq protein receptors.

A

Glutamate

50
Q

Name an NT that stimulates Gi protein receptors.

A

Dopamine

51
Q

What type of protein adds phosphate?

A

Kinase

52
Q

What type of protein removes phosphate?

A

Phosphatase

53
Q

Does all phosphorylation cause a reaction?

A

A lot do - but there are some (limited) examples of phosphorylation inhibiting a reaction.

NSB Lectures (48 decks)

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