Muscle channelopathies and pharmacology

Question 1

3 characteristics of myotonia

Answer 1

1. Lots of A.Ps
2. Hyper-excitability of skeletal muscle
3. Muscle stiffness as a consequence

Question 2

What are the 2 main forms of myotonia

Answer 2

1. Myotonia Congenita- CLC1 mutated

2. Paramyotonia- Nav1.4 mutated

Question 3

How is the RMP different in a person suffering from Myotonia Congenita?

Answer 3

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

Question 4

What is Malignant Hyperthermia?

Answer 4

Autosomal dominant disease
Completely asymptomatic until triggered
Abnormal response to anaesthesia- halothane
80% death rate

Question 5

Symptoms of MH

Answer 5

Sweating
Increased body temp
Hyperkalemia 
Low plasma O2
Tachycardia
Tachypnea

Question 6

What mutations cause MH?

Answer 6

Mutated ryanodine receptor- Gain of function
RyR1 activates CLCR in SR membrane
RyR1 sensitive to Halothane
Halothane- increase in calcium release

Question 7

Ways of treating MH

Answer 7

Dantrolene- inhibits RyR1
IV hydration
Diuretics
NAHCO3
Mechanical hyperventilation

Question 8

What causes Paramyotonia?

Answer 8

Na+ channels do not close properly-
issued with inactivation gate
Depolarisations prolonged
Cold temperature is the trigger

Question 9

What is the treatment of Myotonia?

Answer 9

Mexiletine- Na+ channel blocker

Blocks some A.Ps

Question 10

Sources of tetrodotoxin

Answer 10

*Marine bacteria in a symbiotic relationship with fish, amphibians, fish
Ingestion of puffer fish
Bite from blue ringed octopus

Question 11

Symptoms of tetrodotoxin poisoning (ingestion)

Answer 11

Numbness of lips and tongue
Facial paraesthesia
Nausea
increasing paralysis

Question 12

Symptoms of tetrodotoxin poisoning (bite)

Answer 12

Depends on location of bite

Faster time of death

Question 13

What does TTX block

Answer 13

Na+ channels- inhibits neurotransmission

Question 14

What change in amino acid causes heart Na channels to become sensitive to TTX

Answer 14

Cysteine changed to tyrosine

position 374

Question 15

Sources of dendrotoxins

Answer 15

Snake- mamba family

Question 16

Symptoms of dendrotoxin poisoning

Answer 16

Early weakness/numbness where bitten
Ptosis 
Ophthalmoplegia 
Disphagia
Respiratory failure

Question 17

What effect does dendrotoxin have on neurotransmission?

Answer 17

Inhibits presynaptic K+ channels- no repolarisation
initial excess release of Ach, causing subsequent depletion of Ach
=Problems with muscle control

Question 18

Sources of conotoxin

Answer 18

Cone snails
1000s of different conotoxins
varying lethality

Question 19

Symptoms of conotoxin poisoning

Answer 19

Burning pain
Swelling at site
Numbness
Cardiac and respiratory distress 
Lips become stiff- lethal form
Cramps
Coma