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NSB! > Chemistry and Physiology of the Synapse > Flashcards

Chemistry and Physiology of the Synapse Flashcards

1
Q

There are 2 classes of postsynaptic receptors, what are they called?

  1. ligand gated (ionotrophic) and G-protein coupled (metabotrophic)
  2. ion gated (ionotrophic) and G-protein coupled (metabotrophic)
  3. ligand gated (ionotrophic) and ion gates (metabotrophic)
  4. receptor tyrosine kinase (ionotrophic) and G-protein coupled (metabotrophic)
A
  1. ligand gated (ionotrophic) and G-protein coupled (metabotrophic).
  • ionotrophic = ion sensitive, fast
  • metabotrophic = associated with metabolic pathways, slow
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2
Q

How do ligand gated channels work?

A
  • ligand binds with receptor on ligand gated receptor
  • ligand gated receptor undergoes conformational change creating a pore/channel
  • ions to cross the membrane (creates gradient membrane)
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3
Q

Why are metabotropic receptors given this name?

A
  • the eventual movement of ions through a channel will require one or more metabolic steps
  • GDP to GTP for example to activate the G protein and intracellular pathways
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4
Q

Why are ionotropic receptors given this name?

A
  • once ligand binds ion channels are formed
  • ions can enter or leave the cell
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5
Q

How do G protein coupled channels work?

A
  • ligand binds to binding site
  • G protein inside cell activates intracellular pathway
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6
Q

Do ligand gated (iontropic) or G-protein coupled (metabotropic) receptors have a faster transmission?

A
  • ligand gated channels
  • dont require all the intracellular steps associated with the GPCRs
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7
Q

What does GLuR mean?

A
  • GLu = glutamate
  • R = receptor
  • Glutamate Receptor
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8
Q

What is glutamate?

A
  • an amino acid ingested in the diet
  • functions as an excitatory neurotransmitter
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9
Q

What are the 3 types of ionotropic glutamate receptors, that are defined by the agonist of the receptor?

  1. AMPA (main one), NMDA, Kainate
  2. Na+ channel (main one), NMDA, Kainate
  3. GPCR (main one), NMDA, Kainate
  4. AMPA (main one), K+ channel, Kainate
A
  1. AMPA (main one), NMDA, Kainate
  • AMPA (main excitatory channel)
  • NMDA (has a Mg+ molecule that inhibits it
  • Kainate
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10
Q

AMPA is a glutamate receptor. What happens to the AMPA receptors if glutamate binds with it?

  1. conformational change, opens Na+ channels and re-polarisation
  2. conformational change, opens Na+ channels and hyper-polarisation
  3. conformational change, opens K+ channels and de-polarisation
  4. conformational change, opens Na+ channels and de-polarisation
A
  1. conformational change, opens Na+ channels and de-polarisation
  • the receptor has a conformational change
  • conformational changes makes it specific to Na+ ions
  • action potential occurs at post synaptic neuron
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11
Q

Glutamate NMDA is a glutamate receptor. The NMDA receptor is composed of 2 identical subunits. In addition to glutamate, what else is required to bind with the NMDA receptor to try and initiate an action potential?

  1. glycine
  2. glutathione
  3. gamma-amino-butyric acid
  4. dopamine
A
  1. glycine
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12
Q

Glutamate NMDA is a glutamate receptor. The NMDA receptor is composed of 2 identical subunits. Glutamate and glycine (both neurotransmitters) bind to a subunit each. This can open the channel allowing Ca2+ to flow into the cell. However, this can also be insufficient alone to remove the Mg2+. What else can contribute to NMDA receptors to open?

  1. multiple graded potentials
  2. increased glycine binding
  3. decreased K+ leaving the cell
  4. increased glutamate binding
A
  1. multiple graded potentials
  • multiple NMDA receptors allows the charge to cross the threshold for an action potential
  • charge around NMDA receptor is changed and the Mg2+ inhibitor is removed
  • Ca2+ then flows into the cell creating an action potential
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13
Q

What does GABA stand for and what is it?

A
  • Gamma Aminobutyric Acid
  • a neurotransmitter
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14
Q

GABA can bind to a ligand gated channel that is able to inhibit the post synaptic membrane. How does it do this?

  1. influx of Cl-
  2. opening K+ channels and K+ leaves the cell
  3. closes Na+ channels so Na+ cannot enter the cell
  4. inhibits Na+ channels
A
  1. causes an influx of Cl-
    * results in hyperpolarisation and inhibits action potentials
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15
Q

Where is the acetylcholine (ACh) ionotropic receptor found in the body?

A
  • neuromuscular junction
  • binds with 2 ACh ligands using the 2 a subunits
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16
Q

Which receptor is present in approx. 90% of brain synapses?

  1. NMDA
  2. dopamine
  3. AMPA
  4. tyrosine
A
  1. AMPA receptors
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17
Q

If stimulus has been supplied glutamine will be released into the synaptic cleft and bind to the glutamine receptors AMPA and NMDA receptors. But if the signal is not sufficiently strong what happens with the AMPA and NMDA receptors?

A
  • AMPA receptors are generally stimulated causing small depolarisation
  • NMDA does not open due to Mg2+ blocking the pore
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18
Q

If stimulus has been supplied glutamine will be released into the synaptic cleft and bind to the glutamine receptors AMPA and NMDA receptors. If the signal is sufficiently strong what can happen to the AMPA and NMDA receptors?

A
  • AMPA channels open depolarising the post synaptic neuron (Na+ influx)
  • Mg2+ previously blocking the NMDA channel is removed (N+ and Ca2+ influx)
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19
Q
  • the process where all signals to a neuron are combined prior to generating an action potential, is the definition of ?
  • more inhibitory signals = hyperpolarisation
  • more excitatory signals = depolarisation
A

What is synaptic integration?

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20
Q

Where does the majority of synaptic integration in a neuron occur?

  1. dendrites
  2. pre-synapse
  3. post-synapse
  4. synaptic cleft
A
  1. in dendrites
    - referred to as dendritic integration.
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21
Q

When looking at GABA, what does IPSP refer to?

A
  • _i_nhibitory _posts_ynaptic _p_otential
  • hyperpolarisation occurs (no action potential)
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22
Q

When norepinephrine (a neurotransmitter) binds to its respective ligand binding site on the GPCR (Gas) what is the intracellular pathway to elicit its target reaction of increasing protein phosphorylation?

A
  1. adenylyl cyclase (effector protein) converts ATP into cAMP
  2. cAMP (second messenger) activates protein kinase A
  3. increased protein kinase A (later effectors)
  4. protein kinase A increases protein phosphorylation
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23
Q

When glutamate (a neurotransmitter) binds to its respective ligand binding site on the GPCR (Gq) what is the intracellular pathway to elicit its target reaction of increasing protein phosphorylation and activation of Ca2+ binding proteins?

A
  1. phospholipase C (effector protein) cleaves PiP2 into IP3 and DAG
  2. IP3 (second messenger) binds to sarcoplasmic reticulum, releasing Ca2+ (second messenger)
  3. Ca2+ binds with DAG and activates protein kinase C (pKC)
  4. pKC increases protein phosphorylation and activation of Ca2+ binding proteins
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24
Q

When dopamine (a neurotransmitter) binds to its respective ligand binding site on the GPCR (Gi) what is the intracellular pathway to elicit its target reaction of decreasing protein phosphorylation?

A

inhibits Gas on GPCR

1 - inhibits adenylyl cyclase

2 - causes reduced cAMP and protein kinase A

25
Q

What effect does norepinephrine have on the body?

A
  • causes fight or flight
26
Q

What effect does dopamine have on the body?

A
  • can be inhibitory and excitatory
27
Q

Phosphorylation can do what 2 main things to proteins?

A

1 - turn them on or off

2 - cause conformational change

28
Q

What do protein kinase and protein phosphotases do in relation to phosphorylation?

A
  • kinase = add phosphates (activate and cause protein to change shape)
  • phosphotases = remove phosphates (tases sounds like taking)
29
Q

What are the two types of postsynaptic receptors?

A
  1. Ligand-gated (Ionotropic)
  2. G-protein Coupled (Metabotropic)
30
Q

Describe the events that happen following the binding of a neurotransmitter to a G-protein Coupled receptor…

A
  1. Neurotransmitter Binds
  2. G-protein is activated
  3. Signal modulation (shape change)
  4. Channel opening
  5. Ions cross through the channel
31
Q

Which type of receptors are involved in fast transmission?

A

Ligand-gated ion channels

32
Q

The ions that are permitted to cross the channel protein (essentially the selective ion that channels allow through). is the definition of

A

ion permeability

33
Q

How many ions per unit time cross the central pore of the receptor is the definition of ….

A

ion conductance…

34
Q

In terms of neurotransmitters and conformational change what does dynamics and kinetics mean?

A

It is the neurotransmitter affinity (how well does it bind) and the rate of conformational change and how this determines the longevity of the effect.

35
Q

Which neurotransmitter binds to the receptor is the definition of

A

Ligand Affinity

36
Q

There are three ionotropic Glutamate receptors (GluR) - What are they called?

A

AMPA

NMDA

Kainate

37
Q

Which type of ionotropic receptor in found in around 90% of all brain synapses on the post-synaptic membrane?

A

Glutamate AMPA

38
Q

How many subunits make up the AMPA ionotropic receptor?

A

Four (which form a central pore). These are GluA1, 2x GluA2 and GluA3.

39
Q

Glutamate AMPA has four polypeptide chains that make up its quaternary structure. From this there are three domains (areas of a protein with specific roles) - what are they?

A

Transmembrane Domain (TMD): Acts as a pore as well as a passage for the protein across the membrane

Ligand Binding Domain (LBD): The site where the NT/agonist binds.

N-terminal Domain (ADT or NTD): Domain responsible for post-translational modification

40
Q

Which subunit of AMPA is specific to Na+ and therefore responsible for the depolarisation and the resulting action potential?

A

GluA2 (of which there are two).

This domain causes the receptor to be selective to Na+ ions which causes depolarisation and therefore an excitatory post-synaptic potential. Only if enough channels are activated will an action potential be fired.

41
Q

Glutamate NMDA receptors are made from 2 subunits of which there are two of each. What are these subunits called?

A

GluN1 and GluN2

42
Q

Glutamate NMDA is responsible for the passage of Ca2+ which results in late stage post-synaptic depolarisations. Describe how this channel opens to allow for the passage of Ca2+…

A

Both Glutamate and Glyceine must bind to the receptor in order for the channel to open. Following this there must be repeated depolarisations by AMPA receptors called activity dependant synaptic modification in order to remove a magnesium ion present like a plug in the channel. Once this Mg2+ is removed the Ca2+ influx initiates a biochemical cascade.

43
Q

The ionotropic receptor Glutamate NMDA is responsible for Ca2+ movement causing changes in postsynaptic cells. What does this result in with regards to the human brain?

A

Neuroplasticity and long term memory formation.

44
Q

Like the ionotropic receptor Glutamate AMPA, Glutamate NMDA has three domains. The ATD/NTD domain (N-terminal Domain) has a particularly important function in this protein - what is it?

A

ATD acts as a pH sensor, opening less frequently if the extracellular space has a low pH which protects against ischaemic acidosis.

45
Q

AChR receptors are found where?

A

Neuromuscular junction

46
Q

The AChR receptor is found at the neuromuscular junction. How many subunits make up this receptor?

A

It is composed of the five identical units labelled as alpha, alpha, beta, gamma and delta.

47
Q

AChR binds to TWO acetylcholine ligands using what subunits?

A

The two alpha subunits.

48
Q

This refers to the process of how neurons summate all signals received before generating an action potential.

A

synaptic integration

49
Q

Most synaptic integration occurs at what part of the neuron?

A

Dendrites (and is therefore often referred to as dendric integration).

50
Q

Which receptors are excitatory and which are inhibitory?

1) Glutamate AMPA or Glutamate NMDA
2) GABA

A

1) Excitatory
2) Inhibitory

51
Q

Name the major ions for each type of receptor…#

1) Glutamate AMPA
2) Glutamate NMDA
3) GABA

A

1) Na+ (primarily with some K+)
2) Ca2+ (primarily with some K+ and Na+)
3) Cl-

52
Q

What is the post synaptic potential for each of the following receptor?

A 
Glutamate = Excitatory
GABA = Inhibitory (brain)
Glycine = Inhibitory (spinal cord and brain stem)
Nicotinic = Excitatory at NMJ, excitatory or modulatory in the CNS
Serotonin = Excitatory or modulatory
ATP = Excitatory
52
Q

What is the post synaptic potential for each of the following receptor?

A 
Glutamate = Excitatory
GABA = Inhibitory (brain)
Glycine = Inhibitory (spinal cord and brain stem)
Nicotinic = Excitatory at NMJ, excitatory or modulatory in the CNS
Serotonin = Excitatory or modulatory
ATP = Excitatory
53
Q

Metabotropic receptors are slow response receptors. What does this mean?

A

As opposed to direct ion channel binding, the neurotransmitter binds to a G-protein coupled receptor (GPCR) instead. This results in a G-protein complex forming, this protein is then released and a biochemical cascade initiated.

54
Q

What type of receptor is shown here?

A

Metabotropic receptor (G-protein coupled receptor).

55
Q

Give three examples of second messengers from Gq, Gs and Gi receptors.

A

Gs and Gi = cAMP (although important to remember than Gi is inhibitory to cAMP is inhibited)
Gq = PIP2 (Phospholipase 2 converts PIP2 –> IP3 and DAG)

56
Q

Name the main type of control for proteins which affects their activity or alters its binding…

A

Phosphorylation by protein kinases and dephosphorylation by protein phosphatases

57
Q

name the family & G protein associated with each group

A

Group I = mGluR1+5 (Gq)
Group II = mGluR2+3 (Gi)
Group III = mGluR4,6,7+8 (Gi)

58
Q

Name some metabotropic receptors that arent the usual Glutamate G protein couple receptors…

A

Dopamine Receptors
GABA(B) receptor
muscarinic acetylcholine receptors
noradrenergic and adrenergic receptors
neuropeptide receptors
serotonin receptors

NSB! (53 decks)

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