Chemistry and Physiology of the Synapse

Question 1

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)

Answer 1

1. ligand gated (ionotrophic) and G-protein coupled (metabotrophic)

• ionotrophic = ion sensitive
  
  • metabotrophic = associated with metabolic pathways

Question 2

How do ligand gated channels work?

Answer 2

• 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)

Question 3

Why are metabotropic receptors given this name?

Answer 3

• 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

Question 4

Why are ionotropic receptors given this name?

Answer 4

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

Question 5

How do G protein coupled channels work?

Answer 5

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

Question 6

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

Answer 6

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

Question 7

What does GLuR mean?

Answer 7

• GLu = glutamate
• R = receptor
• Glutamate Receptor

Question 8

What is glutamate?

Answer 8

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

Question 9

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

Answer 9

1. AMPA (main one), NMDA, Kainate

• AMPA (main excitatory channel)
• NMDA (has a Mg+ molecule that inhibits it
• Kainate

Question 10

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

Answer 10

4. 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

Question 11

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

Answer 11

1. glycine

Question 12

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

Answer 12

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

Question 13

What does GABA stand for and what is it?

Answer 13

• Gamma Aminobutyric Acid
• a neurotransmitter

Question 14

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

Answer 14

1. causes an influx of Cl-
   * results in hyperpolarisation and inhibits action potentials

Question 15

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

Answer 15

• neuromuscular junction
• binds with 2 ACh ligands using the 2 a subuntis

Question 16

Which receptor is present in aprox 90% of brain synapses?

1. NMDA
2. dopamine
3. AMPA
4. tyrosine

Answer 16

3. AMPA receptors

Question 17

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?

Answer 17

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

Question 18

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?

Answer 18

• AMPA channels open depolarising the post synaptic neuron (Na⁺ influx)
• Mg²⁺ previously blocking the NMDA channel is removed (N+ and Ca2+ influx)

Question 19

What is synaptic integration?

Answer 19

• the process where all signals to a neuron are combined prior to generating an action potential
• more inhibitory signals = hyperpolarisation
• more excitatory signals = depolarisation

Question 20

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

1. dendrites
2. pre-synapse
3. post-synapse
4. synaptic cleft

Answer 20

1. in dendrites
   - referred to as dendritic integration.

Question 21

When looking at GABA, what does IPSP refer to?

Answer 21

• inhibitory postsynaptic potential
• hyperpolarisation occurs (no action potential)

Question 22

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

Answer 22

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

Question 23

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?

Answer 23

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

Question 24

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?

Answer 24

inhibits Gas on GPCR

1 - inhibits adenylyl cyclase

2 - causes reduced cAMP and protein kinase A

Question 25

What effect does norepinephrine have on the body?

Answer 25

• causes fight or flight

Question 26

What effect does dopamine have on the body?

Answer 26

• can be inhibitory and excitatory

Question 27

Phosphorylation can do what 2 main things to proteins?

Answer 27

1 - turn them on or off

2 - cause conformational change

Question 28

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

Answer 28

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