toxins

Question 1

DEFINE: paraesthesia

Answer 1

abnormal sensation e.g. tingling

Question 2

what leads to death when poisoned with tetrodotoxin?

Answer 2

paralysis of respiratory muscles

Question 3

TTX physiology

Answer 3

1. voltage gated Na+ channels on motor nerve inhibited
2. no neuronal AP
3. reduced ACh release at neuromuscular junction
4. no activation on muscle AChR
5. no muscle AP –> reduced contraction

Question 4

which voltage gated Na+ channels are TTX insensitive?

Answer 4

Nav1.5
Nav1.8
Nav1.9

Question 5

which change in the rat voltage gated Na+ channel type II gives rise to TTX insensitivity

Answer 5

E387Q - glutamate to glutamine in pore region

results in Nav no longer blocked by TTX

Question 6

voltage gated Na+ channel structure

Answer 6

24 TM domains
4 repeats of 6 TM domains
4th domain of each group of 6 domains = voltage sensor
pore regions make up the channel

Question 7

brain and muscle voltage gated Na+ channel

Answer 7

TTX sensitive

tyrosine at position 374

Question 8

heart voltage gated Na+ channel

Answer 8

TTX insensitive

cysteine at position 374

Question 9

how did the Garter snake in Bear Lake develop TTX insensitivity?

Answer 9

1. garter snake with de novo mutation in IV domain of voltage gated Na+ channel sequence -> lost sensitivity to TTX
2. broader range of food to eat so more likely to survive and breed
3. passed on mutation to next generation

Question 10

ptosis

Answer 10

muscles are unable to contract to hold eyelids up - drooping eyelids

Question 11

what are the symptoms experienced after being poisoned with dendrotoxin?

Answer 11

• early weakness/numbness in bitten extremity
• systemic responses experienced in 30 mins to 1 hour
• ptosis
• opthalmoplegia - cannot move eyes well
• disphagia - impact on smooth muscle affecting digestion so difficulty swallowing
• paresis
• respiratory failure leading to death

Question 12

paresis

Answer 12

mild, bodywide paralysis

Question 13

opthalmoplegia

Answer 13

paralysis of eye muscles

Question 14

DTX physiology

Answer 14

1. DTX inhibits voltage gated K+ channels on neuronal membrane
2. delayed repolarisation
3. at 1st instance there is excess release of ACh from pre-synapse -> increased muscle tone
4. ACh depletion
5. failure of subsequent neurotransmission
6. problems with muscle control + paralysis
7. respiratory paralysis –> death

Question 15

which symptoms are associated with lethal cases of conotoxin poisoning?

Answer 15

lips becoming stiff
blurred vision
paralysis
coma

Question 16

how is Cav2.2 involved in pain?

Answer 16

Cav2.2 sits in pre-synaptic membrane of sensory neuron
mediates neurotransmitter release
neurotransmitter signals to post-synaptic membrane
AP triggered in spinal cord + sent to brain to signal pain

Question 17

what is the limitation of using human embryonic kidney cells ectopically expressing Cav2.2 to show the effect of conotoxin on Cav2.2?

Answer 17

ion channels interact with a lot of proteins

normal proteins interacting with Cav2.2 may not be in the human embryonic kidney cell which affects Cav2.2