Cardiac Channelopathies Flashcards
What are two syndromes associated with Cardiac channelopathies
long QT and short QT
What is affected in long and short QT syndromes
changes to ventricular myocyte APs
What interval of the cardiac cycle do LQT and SQT affect
QRS wave to T wave
Which wave changes in QT syndromes
T wave changes
What is the effect of the T wave changing in QT syndromes
repolarisation is accelerated or delayed
What is the ventricular action potential plateau phase mediated by
voltage gated calcium channels
What is the T wave in ventricular APs associated with
repolarisation phase
What is ventricular tachycardia
additional beat - number of contractions in ventricles is increased
What is ventricular fibrillation
fatal - completely un co-ordinated contraction of ventricular myocytes
What can occur in long QT
ectopic beat
What are the implications of QT syndromes
signals dont spread where they should
What is a form of tachycardia highly associated with ventricular fibrillation - death
torsades de pointes
What is torsases de pointes associated with in an ECG
twisting motion
Mutations in what channels cause Long QT
KCNQ1, SCN5A, KCNE1, CACNA1C
What is KCNQ1
voltage gated potassium channel
What mutation affects KCNQ1 in Long QT
loss of function
What is SCN5A
sodium channel
What does SCN5A mediate
depolarisation of ventricular action potentials
What mutation affects SCN5A in long QT
gain of function
What is KCNE1
protein - potassium channel regulator
What is the function of KCNE1
makes sure KCNQ1 is working properly
What mutation affects KCNE1 in long QT
loss of function
What is CACNA1C
main L type calcium channel
What is the function of CACNA1C
maintains plateau phase of APs
What mutation affects CACNA1C in long QT syndrome
gain of function mutations
Where do the majority of mutations occur in KCNQ1 in long QT
transmembrane spanning domains, pore region
What other organ can be affected by mutations in Q1
ear
Where are stria vascularis found
epithelial cells in the ear
What is the function of stria vascularis
secrete potassium into the endolymph
What is the affect of mutated Q1 E1 complex in the ear
deafness - Reissner’s membrane collapses due to no endolymph
Describe the 3 key mutations in Long QT
gain of function in sodium and calcium channels, loss of function in potassium channels
What is delayed in long QT
start of repolarisation
How is long QT treated
B blockers, Atenolol
What is atenolol
B1 selective antagonist
What is the effect of atenolol
reduces strength of contraction and rate of firing at SA node
What puts you at higher risk of arthymia
increases heart rate
What are the symptoms of short QT
reduced QT interval, arrhythmias, palpitations, fainting, death
Describe the genes mutated in short QT
same as long QT but mutated in opposite ways
What is the effect of loss of function mutations in calcium channels
plateau in action potential is not maintained - repolarisation occurs fastr
What is the effect of gain of function mutations in potassium channels
channels overactive - drive repolarisation faster and earlier
What mutations are associated with short QT
loss of function in calcium channels, gain of function in potassium channels
What do the mutations associated with short QT cause
accelerated timing of repolarisation
What is the treatment for short QT
implant defibrillator, quinidine
