Neuronal and muscle toxins I and II Flashcards
What is the source of tetrotoxin?
WRITE ANSWER AND CHECK WITH A4 PAPER
What are the symptoms of tetrotoxin?
WRITE ANSWER AND CHECK WITH A4 PAPER
What are the treatments of tetrotoxin?
WRITE ANSWER AND CHECK WITH A4 PAPER
Where does teterotoxin act?
What does this cause?
WRITE ANSWER AND CHECK WITH A4 PAPER
What determines if channels are ttx sensitive or insensitive?
What are the 3 pieces of evidence for this?
WRITE ANSWER AND CHECK WITH A4 PAPER
What determines if channels are ttx sensitive or insensitive?
What are the 3 pieces of evidence for this?
WRITE ANSWER AND CHECK WITH A4 PAPER
What are the symptoms of injection with dendrotoxins?
WRITE ANSWER AND CHECK WITH A4 PAPER
What is the physiology of DT?
WRITE ANSWER AND CHECK WITH A4 PAPER
Why is it thought that CT can be used as in the treatment of pain?
WRITE ANSWER AND CHECK WITH A4 PAPER
What is the pathway of pain?
WRITE ANSWER AND CHECK WITH A4 PAPER
What channels are the targets of CT?
Nav1.8
Cav2.2
Where is Cav2.2 found?
What does it mediate?Why?
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
Where in the human is Cav2.2 expressed?
In human embryonic kidney cells (HEK)
What is Eu1.6?
A conotoxin which inhibits Cav2.2 channels in HEK cells
What happens if add Eu1.6 to HEK cell with an ARTIFICIALLY EXPRESSED Cav2.2 channel?
What does this mean in terms of pain?
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)
What are the disadvantages of looking at the effect of Eu1.6 on Cav2.2 channels in HEK?
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
Where is Cav2.2 NORMALLY expressed?
In rat DRG cells
Why is Barium used as a charged carrier when looking at Ca2+ channels?
Normally, Ca2+ travels through the channel and feeds back onto the channel –> inactivating it
Ba2+ DOESN’T feedback on the channel
–> more STABLE current
What happens when Eu1.6 is added to rat DRG cells?
Block 1/3 of the Nav channels –> reducing the release of neurotransmitters
–> Current increase in the presence of pain is SMALLER compared to control
Describe the rat partial nerve ligation technique
Model of pain and how Eu1.6 can be used to reduce the feeling of pain
Describe the rat partial nerve ligation technique
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)
Which 3 types of rat is the partial nerve ligation technique done with?
1) Some animals - injection of saline
2) Some - POSITIVE control (morphine and gabapentin)
3) Some - treatment with Eu1.6
Why is the ‘positive control’ done in the rat partial nerve ligation technique?
Drugs that are KNOWN to relieve pain
What was the results of the rat partial nerve ligation technique?
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
