Cardiac Channelopathies

Question 1

What are the symptoms of long QT syndrome?

Answer 1

Fainting, dizziness, heart palpitations, congenital deafness

Question 2

How does a long QT action potential differ from a normal ventricular action potential?

Answer 2

A long QT action potential is an action potential that is 0.45s or greater whereas a normal ventricular AP is roughly 0.36s

Question 3

What are the origins of the symptoms of long QT syndrome?

Answer 3

Triggered activity occurs which leads to ectopic beats, resulting is ventricular tachycardia and ventricular fibrillation
Re-enterant excitation leads to spatial and temporal dispersion which leads to ventricular tachycardia and ventricular fibrillation

Question 4

What are some of the K+ channel mutations that lead to long QT syndrome?

Answer 4

LQT1 - KCNQ1 encodes for Kv7.1a channel, loss of function mutation affects the Iks channel *30-35% of long QT due to this mutation
LQT2 - KCNH2 encodes Kv11.1a, loss of function mutation affects Ikr channel *25-30% of LQTS
LQT4 - ANK2 encodes Ankyrin B, loss of function mutation affects Ik channel *1-2% of LQTS
LQT5 - KCNE1 encodes for MinK, loss of function of regulator of Iks, *1% of LQTS

Question 5

What are some of the Na+ channel mutations that lead to long QT syndrome?

Answer 5

LQT3 - SCN5A encodes Nav1.5a channel, gain of function mutation *5% of LQTS - deletion of three amino acids in the linker region
LQT4 - ANK2 encodes Ankyrin B, loss of function mutation affects Ina channel *1-2% of LQTS

Question 6

What are the treatments for long QT syndrome?

Answer 6

Beta blockers such as atenolol that are B1 selective antagonists

Question 7

What are the symptoms of short QT syndrome?

Answer 7

Arrhythmias, palpitations, syncope

Question 8

How does a short QT action potential differ from a normal ventricular action potential?

Answer 8

Short QT action potentials are 0.34s or less compared to approximately 0.36s of a normal ventricular action potential

Question 9

What are the causes of short QT syndrome?

Answer 9

SQT1 - KCNH2 gain of function mutation in Kv11.1a channels, Ikr
SQT2 - KCNQ1 gain of function in Kv7.1a channels, Iks
SQT3 - KCNJ2 gain of function in Kir2.1a, Ik1
SQT4 - CACNA1C loss of function in Cav1.2a, Ica
SQT5 - CACNB2 loss of function in Cav1.2b2, Ica

Question 10

What are the treatments for short QT syndrome?

Answer 10

Defibrillator
Quinidine (K+ channel blocker)