Cardiac Channelopathies Flashcards
What are the main groupings of sudden cardiac death?
What are the causes of this?
Long or short QT syndrome
Changes to ventricular myocyte action potentials and ion channel mutations in the ventricles
What are the parts of the normal ECG?
What do these represent?
P wave - atrial depolarisation
QRS - ventricular depolarisation
T - ventricular REpolarisation
What is the QT interval?
From the START of the QRS to the END of the T
Why is atrial REpolarisation not shown on the ECG?
Happens at the SAME TIME as ventricular deoplarisation
So is MASKED by the QRS wave
What is long QT?
DELAY of the T wave
Defect in the ventricle REPOLARISATION
Prolonged QT interval
What is short QT?
SPEEDING up of the START of the T wave (happens too early)
What channels are involved in the QT interval?
Voltage gated Ca2+ channels
Na+ channels
K+ channels
What are the implications of altered QT intervals?
Increase risk of VENTRICULAR TACHYCARDIA
What is ventricular tachycardia?
What does increase the risk of?
- Increase in the firing rate of action potentials
- Increase in the number of CONTRACTIONS of the ventricles
Risk factor of going into VENTRICULAR FIBRILLATION
What is ventricular fibrillation?
Contraction of the ventricles in an UNCONTROLLED manner
What is triggered activity?
Changes in the electrical signals in the cells:
- Depolarisation in the cells reach threshold at a time point in the cardiac cycle that are NOT normally expected
- EXTRA beat
- VENTRICULAR TACHYCARDIA if the cells have many extra beats
- At risk of VF
What is re-entrant excitation?
Why is it called ‘re-entrant’?
Seen in clusters of of myocytes (not all of them):
- Electrical activity from the extra beat SPREADS from the effected cells to adjoining cells
- Different LAYERS impacted
- Causes FURTHER spread of contraction (effecting the normal spread)
Called re-entrant because the AP fired from the abnormal cells FEEDBACK onto the other cells, causing them to contract
What impacts does re-entrant excitation have?
- Spatial (in space)
- Temporal (in time)
What happens after the abnormal cells fire what happens to them?
What does this mean?
They become REFRACTORY
Unable to respond to a NORMAL signal coming down from the node
What are the symptoms of long QT syndrome?
- Syncope (fainting)
- Sudden death (Torsades de pointes - forms VT)
What is the inheritance of long-QT?
- 12 different forms of gene changes
- Gain of function/loss of function
What are the different types of long-QT?
How are they different?
1) Self-limiting episode
- ECG goes back to NORMAL
2) Episode leading to ventricular fibrillation
- ECG doesn’t go back to normal
How many different mutations leading to LQT?
12 types
What causes LQT1?
LOSS OF FUNCTION mutation in Kv7.1alpha channel (KCNQ1 gene):
- K+ channel
- In the alpha subunit
What is LQT1?
Long QT type 1
What is the Kv7.1 alpha channel associated with?
The Iks current
What cause LQT3?
GAIN OF FUNCTION mutation in Nav1.5alpha channel (SCN5A gene):
What is the Nav1.5alpha channel associated with?
Ina current
What causes LQT5?
Mutation in MinK protein (KCNE1 gene)
What is MinK protein?
Regulator of K+ Kv7.1alpha
What causes LQT8?
GAIN OF FUNCTION mutation in Cav1.2alpha channel (CACNA1C)
What is Cav1.2aplha involved with?
Ica current
Why is it not a massive impact if there is a mutation in K+ channel?
Not a massive impact as there are many K+ channels
If a mutation in one channel, other channels can subserve the function
What is the structure of the KVLQ1 channel?
4 subunits come together to form a functional K+ channel
Why are the mutations that could be present in the KVLQ1 channel?
- SOME are autosomal dominant and SOME are autosomal recessive
- SOME mutations in the C terminus
- MOST mutations in the membrane spanning domains
- Loss of function in Q1 potassium channel or its regulator
What is the Q1 potassium channel important in?
What happens if there is a mutation in this channel?
Repolarisation
- Slows repolarisation
- QT interval extends
How are forms of LQT syndromes are associated with deafness?
K+ channels in the stria vascularis - concentrate endolymph
Through the Q1/E1 complex
What mutations occur to Na+ and Ca2+ channels in LQT?
What does this cause?
Why?
Gain of function mutations
Causes:
- Prolongation of the plateau phase
- Delay of the repolarisation phase
As these channels are normally open and cause depolarisation - but stay open for LONGER
What are the treatments for LQT?
Example?
Beta blockers
Example: atenolol
