Neuronal and muscle toxins I and II

Question 1

What is the source of tetrotoxin?

Answer 1

WRITE ANSWER AND CHECK WITH A4 PAPER

Question 2

What are the symptoms of tetrotoxin?

Answer 2

WRITE ANSWER AND CHECK WITH A4 PAPER

Question 3

What are the treatments of tetrotoxin?

Answer 3

WRITE ANSWER AND CHECK WITH A4 PAPER

Question 4

Where does teterotoxin act?

What does this cause?

Answer 4

WRITE ANSWER AND CHECK WITH A4 PAPER

Question 5

What determines if channels are ttx sensitive or insensitive?

What are the 3 pieces of evidence for this?

Answer 5

WRITE ANSWER AND CHECK WITH A4 PAPER

Question 6

What determines if channels are ttx sensitive or insensitive?

What are the 3 pieces of evidence for this?

Answer 6

WRITE ANSWER AND CHECK WITH A4 PAPER

Question 7

What are the symptoms of injection with dendrotoxins?

Answer 7

WRITE ANSWER AND CHECK WITH A4 PAPER

Question 8

What is the physiology of DT?

Answer 8

WRITE ANSWER AND CHECK WITH A4 PAPER

Question 9

Why is it thought that CT can be used as in the treatment of pain?

Answer 9

WRITE ANSWER AND CHECK WITH A4 PAPER

Question 10

What is the pathway of pain?

Answer 10

WRITE ANSWER AND CHECK WITH A4 PAPER

Question 11

What channels are the targets of CT?

Answer 11

Nav1.8

Cav2.2

Question 12

Where is Cav2.2 found?

What does it mediate?Why?

Answer 12

In the SENSORY neuron (that senses pain)
In the second neuron in the spinal cord that signals to the brain

Mediates:

• Fusion of the vesicles containing neurotransmitter to the presynaptic neuron
• In order to PROPAGATE pain to the brain

Question 13

Where in the human is Cav2.2 expressed?

Answer 13

In human embryonic kidney cells (HEK)

Question 14

What is Eu1.6?

Answer 14

A conotoxin which inhibits Cav2.2 channels in HEK cells

Question 15

What happens if add Eu1.6 to HEK cell with an ARTIFICIALLY EXPRESSED Cav2.2 channel?

What does this mean in terms of pain?

Answer 15

Size of the currents through the Cav2.2 channel are smaller due to:

• Blockage of Cav2.2 by Eu1.6 –> stops Ca2+ through the channel
• Lower intracellular Ca2+
• Less vesicle fusion and neurotransmitter release
• Less likely to trigger and action potential in the postsynaptic membrane in the spinal cord (which propagates the signal to the brain)

Question 16

What are the disadvantages of looking at the effect of Eu1.6 on Cav2.2 channels in HEK?

Answer 16

Cav2.2 channels are not NORMALLY expressed in the HEK:

• Proteins in the HEK may interact with the channel and change the function/blockage of the channel

Question 17

Where is Cav2.2 NORMALLY expressed?

Answer 17

In rat DRG cells

Question 18

Why is Barium used as a charged carrier when looking at Ca2+ channels?

Answer 18

Normally, Ca2+ travels through the channel and feeds back onto the channel –> inactivating it

Ba2+ DOESN’T feedback on the channel
–> more STABLE current

Question 19

What happens when Eu1.6 is added to rat DRG cells?

Answer 19

Block 1/3 of the Nav channels –> reducing the release of neurotransmitters
–> Current increase in the presence of pain is SMALLER compared to control

Question 20

Describe the rat partial nerve ligation technique

Answer 20

Model of pain and how Eu1.6 can be used to reduce the feeling of pain

Question 21

Describe the rat partial nerve ligation technique

Answer 21

Model of pain and how pharmacological intervention can be used to reduce the feeling of pain:

• Rat is anaesthetised
• Sciatic nerve is exposed
• 1/3 of sciatic nerve is TIED off –> changing the sensitivity to pain
• Apply a KNOWN amount of pressure to the paw until withdrawal
  (withdrawal is a MEASURE of pain)

Question 22

Which 3 types of rat is the partial nerve ligation technique done with?

Answer 22

1) Some animals - injection of saline
2) Some - POSITIVE control (morphine and gabapentin)
3) Some - treatment with Eu1.6

Question 23

Why is the ‘positive control’ done in the rat partial nerve ligation technique?

Answer 23

Drugs that are KNOWN to relieve pain

Question 24

What was the results of the rat partial nerve ligation technique?

Answer 24

BEFORE treatment - all 3 groups withstood the SAME threshold

Saline - NO change

Postive control and Eu1.6 groups:

• Able to withstand a HIGHER force
• Affect wears off to pre-injection level when the drug wears off

Question 25

What was the results of the rat partial nerve ligation technique?

Answer 25

BEFORE treatment - all 3 groups withstood the SAME threshold

Saline - NO change

Postive control and Eu1.6 groups:

• Able to withstand a HIGHER force
• Affect wears off to pre-injection level when the drug wears off

Question 26

Where are tarantula toxins formed?

Answer 26

• MANY different tarantulas –> MANY different toxins

- MOST but not all target DIFFERENT ion channels

Question 27

Which tarantula toxin inhibits Na+ channels?

What is this thought to have a use in? Why?

Answer 27

Tp1a toxin and Gp-Tx-1 toxin –> inhibits Nav1.7 channels

Thought to have a role in pain therapy:

• Nav1.7 is important in generating AP in the sensory neuron that synapses with another neuron in the spinal cord that takes the pain signalling to the brain

Question 28

At what does dos the Tp1a toxin block the Na2+ channels MAXIMALLY?

Answer 28

10nm

Question 29

What happens if the Nav1.7 channels in the sensory neuron are ACTIVATED?

What toxin does this?

Answer 29

MIMICS pain:

• Increases AP firing
• Current through the channels is the SAME but the channels stay open for longer –> more likely to get AP

OD1 (Scorpion toxin) does this

Question 30

What toxin can be used as a pain model?

Why?

How?

Answer 30

OD1 - ACTIVATES Nav channels in the sensory neuron:

• Increasing AP firing
• Leading to pain in the paw of the mouse
• -> Withdrawal, shaking and licking (behaviour can be quantified)

Can then add tarantula toxin to see if reduces the pain:

• Show at higher concentrations –> LESS spontaneous behaviours
• -> BLOCKS pain response