Channelopathies Flashcards
What does the QT interval represent?
The time taken for electrical action and inactivation of the ventricles.
What are the three most common types of LQT syndrome and what is their associated mutation?
LQT1 = caused by a mutation in the KCNQ1 voltage-gated potassium channel.
LQT2 = caused by a mutation in the hERG voltage-gated potassium channel.
LQT3 = caused by a mutation in the NaV1.5 voltage-gated sodium channel.
Which channel proteins co-assemble to form the slow delayed rectifying K+ (Iks) current that contributes to the repolarisation of cardiac action potentials.
KCNQ1 and KCNE1
How is LQT syndrome characterised?
A prolonged QT interval due to delayed repolarisation of the heart.
What causes repolarisation of the cardiac action potential?
The opening of potassium ion channels and the efflux of K+ ions.
What happens during the QT interval?
Ventricular action potentials.
What causes Jervell and Lange-Nielsen Syndrome and why?
A loss of function mutation in KCNQ1 or KCNE1.
As the Endolymph requires a high concentration of K+ for the mechano-transduction of soundwaves, mutations in these proteins limit the secretion of K+ into the Endolymph, and thus cause hearing loss.
What is Lange-Nielsen Syndrome?
A type of Long QT syndrome associated with sensorineural hearing loss.
How is the exocytosis of insulin-containing granules in β-cells brought about?
High levels of ATP in the β-cell causes the K-ATP channels to close. This causes depolarisation of the membrane and the subsequent opening of Ca2+ channels. It is the influx of Ca2+ into the cell that triggers exocytosis of the insulin-containing vesicles.
How does Sulphonylureas act as an anti-diabetic drug?
It causes closure of the K-ATP channels, to stimulate depolarisation of the β-cells and secretion of insulin.
What is Familial Persistent Hyperinsulinaemic Hypoglycemia of Infancy (PHHI)?
It is a disorder of glucose homeostasis, characterised by unregulated insulin secretion and hypoglycaemia.
What causes Familial Persistent Hyperinsulinaemic Hypoglycemia of Infancy (PHHI) and why?
Mutations in SUR1 and K-ATP (Kir6.2).
This leads to the inability of high ADP levels opening K-ATP channels, resulting in continuous β-cell depolarisation, high intracellular Ca2+ levels, and thus continuous insulin secretion.
How does Diazoxide act as a drug to treat Hypoglycaemia?
It causes the K-ATP channels to open, which causes hyperpolarisation of the cell membrane. This results in inhibited insulin secretion and thus an increase in blood glucose.
How does Tolbutamide acts as a drug to treat diabetes?
It causes the K-ATP channels to open, which causes depolarisation of the cell membrane. This promotes insulin secretion, and thus a decrease in blood glucose.
What causes Cystic Fibrosis and why?
A mutation in the CFTR (Cl-) channel/gene.
A defect in this channel limits osmosis and causes the thickening of secreted mucus.
What causes Myasthenia gravis?
The binding of an antibody to Acetylcholine Receptors, which activates a membrane attack complex that destroys the neuromuscular junction. This means Acetylcholine can no longer bind to the receptor to stimulate contraction of the muscles.
How does the activation of the Acetylcholine receptors cause muscle contraction?
Its activation causes depolarisation of the cell membrane. This causes the Ca2+ channels to open and the influx of Ca2+ ions, and thus muscle contraction.
What is the function of Agrin?
Agrin binds to the muscle-specific tyrosine kinase (MuSK) located at the post-synaptic membrane of the NMJ. Its binding triggers the clustering of the acetylcholine receptors so that they are positioned correctly to receive acetylcholine signals.
How do the anti-epileptic drugs, phenytoin, carbamazepine and Iamotriginine work to treat epilepsy?
They work by blocking voltage-gated sodium channels.
How do point mutations in voltage-gated sodium channels contribute to epilepsy?
They cause a gain-of-channel function that will lead to excessive neuronal activity in the brain.
