Muscle channelopathies and pharmacology Flashcards
(19 cards)
3 characteristics of myotonia
- Lots of A.Ps
- Hyper-excitability of skeletal muscle
- Muscle stiffness as a consequence
What are the 2 main forms of myotonia
- Myotonia Congenita- CLC1 mutated
2. Paramyotonia- Nav1.4 mutated
How is the RMP different in a person suffering from Myotonia Congenita?
RMP more positive than normal
Due to loss of function of chloride channels
Loss of Cl- contribution to VM
Only need small depol to trigger an A.P
=Increased excitability of skeletal muscle
What is Malignant Hyperthermia?
Autosomal dominant disease
Completely asymptomatic until triggered
Abnormal response to anaesthesia- halothane
80% death rate
Symptoms of MH
Sweating Increased body temp Hyperkalemia Low plasma O2 Tachycardia Tachypnea
What mutations cause MH?
Mutated ryanodine receptor- Gain of function
RyR1 activates CLCR in SR membrane
RyR1 sensitive to Halothane
Halothane- increase in calcium release
Ways of treating MH
Dantrolene- inhibits RyR1 IV hydration Diuretics NAHCO3 Mechanical hyperventilation
What causes Paramyotonia?
Na+ channels do not close properly-
issued with inactivation gate
Depolarisations prolonged
Cold temperature is the trigger
What is the treatment of Myotonia?
Mexiletine- Na+ channel blocker
Blocks some A.Ps
Sources of tetrodotoxin
*Marine bacteria in a symbiotic relationship with fish, amphibians, fish
Ingestion of puffer fish
Bite from blue ringed octopus
Symptoms of tetrodotoxin poisoning (ingestion)
Numbness of lips and tongue
Facial paraesthesia
Nausea
increasing paralysis
Symptoms of tetrodotoxin poisoning (bite)
Depends on location of bite
Faster time of death
What does TTX block
Na+ channels- inhibits neurotransmission
What change in amino acid causes heart Na channels to become sensitive to TTX
Cysteine changed to tyrosine
position 374
Sources of dendrotoxins
Snake- mamba family
Symptoms of dendrotoxin poisoning
Early weakness/numbness where bitten Ptosis Ophthalmoplegia Disphagia Respiratory failure
What effect does dendrotoxin have on neurotransmission?
Inhibits presynaptic K+ channels- no repolarisation
initial excess release of Ach, causing subsequent depletion of Ach
=Problems with muscle control
Sources of conotoxin
Cone snails
1000s of different conotoxins
varying lethality
Symptoms of conotoxin poisoning
Burning pain Swelling at site Numbness Cardiac and respiratory distress Lips become stiff- lethal form Cramps Coma
