toxins Flashcards
DEFINE: paraesthesia
abnormal sensation e.g. tingling
what leads to death when poisoned with tetrodotoxin?
paralysis of respiratory muscles
TTX physiology
- voltage gated Na+ channels on motor nerve inhibited
- no neuronal AP
- reduced ACh release at neuromuscular junction
- no activation on muscle AChR
- no muscle AP –> reduced contraction
which voltage gated Na+ channels are TTX insensitive?
Nav1.5
Nav1.8
Nav1.9
which change in the rat voltage gated Na+ channel type II gives rise to TTX insensitivity
E387Q - glutamate to glutamine in pore region
results in Nav no longer blocked by TTX
voltage gated Na+ channel structure
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
brain and muscle voltage gated Na+ channel
TTX sensitive
tyrosine at position 374
heart voltage gated Na+ channel
TTX insensitive
cysteine at position 374
how did the Garter snake in Bear Lake develop TTX insensitivity?
- garter snake with de novo mutation in IV domain of voltage gated Na+ channel sequence -> lost sensitivity to TTX
- broader range of food to eat so more likely to survive and breed
- passed on mutation to next generation
ptosis
muscles are unable to contract to hold eyelids up - drooping eyelids
what are the symptoms experienced after being poisoned with dendrotoxin?
- 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
paresis
mild, bodywide paralysis
opthalmoplegia
paralysis of eye muscles
DTX physiology
- DTX inhibits voltage gated K+ channels on neuronal membrane
- delayed repolarisation
- at 1st instance there is excess release of ACh from pre-synapse -> increased muscle tone
- ACh depletion
- failure of subsequent neurotransmission
- problems with muscle control + paralysis
- respiratory paralysis –> death
which symptoms are associated with lethal cases of conotoxin poisoning?
lips becoming stiff
blurred vision
paralysis
coma
how is Cav2.2 involved in pain?
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
what is the limitation of using human embryonic kidney cells ectopically expressing Cav2.2 to show the effect of conotoxin on Cav2.2?
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
