Ion Channels III

Question 1

Why do ion channels not work?

Answer 1

• Hereditary (Passed down via genetics)

- Acquired (Obtained from environmental factors)

Question 2

Give an example of a disorder where ion channels do not work.

Answer 2

HERG - This is where the potassium channels do not work and therefore, heart problems occur.
This results in the QT syndrome.

Question 3

How do local anaesthetics work?

Answer 3

These block sodium channels and therefore, nerve transmission is paused.
These drugs can also be given to patients with heart problems.

Question 4

Name some common local anaesthetics.

Answer 4

• Lidocaine
• Lignocaine
• Benzocaine
• Tetracaine
• Bupivacaine

Question 5

What diseases are associated with voltage - gated sodium channels?

Answer 5

Myotonias (stiffness of the skeletal muscle.)
Paralysis
Epilepsy
LQT3 type arrhythmia

Question 6

Give an example of a sodium channel blocker.

Answer 6

Tetrodotoxin = This is a poison found in pufferfishes.
These inhibit the firing of action potentials and therefore, NO action potential is generated.
This toxin causes problems to the cardiac / skeletal / nerve tissue.

Question 7

What are some diseases associated with mutations to voltage - gated sodium channels?

Answer 7

Myotonias (stiffness of the skeletal muscle)
Paralysis
Epilepsy
LQT3 type arrhythmia

Question 8

What is the most common mutation which results in myotonias?

Answer 8

Inactivation component of acceptor site.

Sodium Channel is still open and therefore, the ions still flow through

Question 9

What is the most common mutation which results in LQT3 type arrhythmia?

Answer 9

There is a triple AA deletion in the inactivation loop.

Question 10

What do the mutations cause in the heart?

Answer 10

Depolarisation is harder.
There is a longer action potential and therefore, increased excitation.
In skeletal muscles -> there is stiffness or paralysis.

Question 11

What happens when venom of spiders / wasps / snakes / scorpions gets into the body?

Answer 11

There is a greater sodium flow coming in and thus, hyper - intense activity can occur. This leads to the failure of the heart.

Question 12

What is a mutation within KCNQ potassium channels?

Answer 12

KCNE subunits alter the biophysics and the pharmacology too.
This results in delayed activation or little inactivation alongside uneven tissue distribution.

Question 13

What diseases arise with a mutated KCNQ potassium channel?

Answer 13

LQT1 / Epilepsy / Deafness

Inner Ear / Cardiac Muscle / Neuron are affected.

Question 14

What is a key heart problem which occurs due to the KCNQ mutation?

Answer 14

KCNQ1 contributes to the late depolarising current of the cardiac action potential.
This is known as Long QT Syndrome.

Question 15

List the two syndrome caused by KCNQ1 (apart from Long QT Syndrome)

Answer 15

Romano - Ward Syndrome = Autosomal Dominant.
Jervall - Lange - Nielsen Syndrome = Recessive form
Leads to associated deafness.

Question 16

Why does epilepsy occur?

Answer 16

When the K+ channels are blocked = there is a surge of action potentials.

Question 17

What does KCNQ2 mutations underlie?

Answer 17

Causes head problems.

• Benign familial neonatal seizures.
• Peripheral nerve hyper excitability / neuromyotonia.

Question 18

What diseases occurs due to a protein trafficking mutation?

Answer 18

Cystic Fibrosis.

Question 19

Explain the protein trafficking mutation.

Answer 19

Protein Trafficking is whereby ion membranes are born and activated by intracellular ligands.
The ion channel does not get to the membrane and thus, there is a major issue.

Question 20

What is the incomplete / loss of trafficking mutation called?
Give an example.

Answer 20

CFTR.

An example is Delta F308

Question 21

What are the 3 reasons why ion channels are mutated?

Answer 21

Incomplete Activity.
Reduced Activity.
Loss of trafficking.