Channels and Channelopathies

Question 0

Name three drugs that target ion channels?

Answer 0

Novartis’ Tegretol for control of partial seizures in epilepsy, works by blocking sodium channels. Voltage-gated calcium ion channel inhibitor for angina. ATP sensitive potassium ion channel inhibitor for diabetes.

Question 1

What do ion channels allow?

Answer 1

Flow of ions down their electrochemical gradient.

Question 2

What are congenital and acquired channelopathies?

Answer 2

Congenital: resulting from a mutation or mutations in the encoding genes.
Acquired: resulting from autoimmune attack, drug effect, toxin on an ion channel.

Question 3

What does tetrodotoxin do?

Answer 3

Blocks action potential nerves by binding to the voltage-gated, fast sodium ion channels in nerve cells.

Question 4

What did tetrodotoxin cause?

Answer 4

Paraestheisa of the lips/ tongue, sweating, headache, weakness, lethargy, tremor, paralysis, cyanosis, aphonia, dysphagia, seizures, dyspnea, bronchorrhea bronchospasm, respiratory failure and CV disease.

Question 5

What does dendrotoxin do?

Answer 5

Blocks voltage-gated potassium channels in neuronal tissue, prolonging action potential duration as it increases acetylcholine release at neuromuscular junction.

Question 6

What does dendrotoxin cause?

Answer 6

Results in muscle hyper excitability and convulsive symptoms.

Question 7

What does terfenadine cause?

Answer 7

Prolonged ventricular repolarisation and an increase in ventricular arrhythmias.

Question 8

What is the mutation in CF?

Answer 8

A mutation in the gene for the protein CF transmembrane conductance (CFTR). Most common is delta F508, loss of phenylalanine at 508.

Question 9

What are the symptoms of CF?

Answer 9

Primarily affects the lungs, thick mucus deposit. Also affects the sinuses, skin, liver, pancreas, intestines and reproductive organs.

Question 10

What cause the thick secretions in CF?

Answer 10

Abnormal transport if calcium and sodium lime across the epithelium.

Question 11

What channels do insulin disorders involve?

Answer 11

ATP-sensitive potassium channels in pancreatic beta cells.

Question 12

What is profound neonatal diabetes?

Answer 12

Type 2 diabetes after birth which is due to over active ATP-sensitive potassium channels.

Question 13

What is long QT syndrome?

Answer 13

Delayed repolarisation of the heart following a heartbeat.

Question 14

What does long QT syndrome cause?

Answer 14

Seizures, sudden cardiac death,

Question 15

What is the mutation that causes long QT syndrome?

Answer 15

Several genes which encode the duration of ventricular action potential, lengthening the QT interval. Common is a mutation in the humans ether-a-go-go-related gene (HERG) which encodes a voltage-gated potassium channel.

Question 16

What venom from the cone snail can be used as a therapeutic agent?

Answer 16

Ziconotide (Prialt) a synthetic peptide of a conotoxin which blocks voltage-gated calcium channels of the spinal cord which inhibits the pain signal transmission.

Question 17

What is the importance of ion channels?

Answer 17

Underly action potentials, key in muscle contraction, transport of nutrients and ions through the epithelium, T-cell activation in the immune response and pancreatic beta-cell insulin release.

Question 18

How can ion channels be classified?

Answer 18

By its ion selectivity sequence.

Question 19

What are the two types of ion channels?

Answer 19

Voltage or ligand gated

Question 20

How do ion channels work?

Answer 20

Multiple subunits form a pore which usually has hydrophobic residues lining it and a typically charges region which acts as the specificity filter.

Question 21

Describe some ion channels that are used as drug targets?

Answer 21

Anti-epileptic drugs are usually sodium ion channel blockers, angina is treated with voltage-gated calcium ion channel inhibitors and diabetes with ATP sensitive potassium ion channel inhibitor.

Question 22

What is patch-clamping used for?

Answer 22

To record ion channel activity.

Question 23

How does patch-clamping work?

Answer 23

Use a glass pipette to make a tight contact with membrane forming a high resistance seal, suction is then applied to disrupt the membrane and allow the interior of the pipette to be continuous with the cytoplasm of the cell so that measure mr of electrical potentials and currents can be made for the entire cell.