Lecture 6 Flashcards
What is SIDS
Sudden infant death syndrome - unexplained by previous history and where post-mortem fails to demonstrate an adequate cause of death.
In which age group is SIDS particularly prevalent
<1 yr of age
What was the back to sleep campaign
1992 - told parents to put babies on their backs to sleep and not in prone position which is a risk factor of SIDS.
Give 4 possible causes of SIDS
Immunological polymorphisms
Autonomic disorders
Metabolic disorders
Cardiac ion channel mutations
What was the difference in QT interval in SIDS babies and normal babies
Average for SIDS babies lied at the upper limit of 2 standard deviations above the mean of normal babies QT interval.
In which genes were mutations found in SIDS babies
SCN5A, KCNQ1, KCNH2, CAV3, KCNE2
Were the mutations in the SCN5A gene localised to one region or spread across the resultant protein
Spread throughout the protein.
What is SCN5A
Gene for sodium voltage gated channel alpha subunit
When looking at the IV curves for the different mutants of SCN5A what changes could be identified
Very little differences, subtle ones in activation/inactivation
What mutation caused a slower inactivation of the SCN5A channel
F1486L mutation of a highly conserved phenylalanine in the ball and chain mech - linker region III-IV so lost its fast inactivation.
When looking at inactivation of the SCN5A mutant channels, what was surprising
A number of mutations induced faster inactivation, so why did the SIDS baby experience long QTS
What was the difference in the amount of inactivation in WT compared to mutant SCN5Achannels
Inactivation may have been faster in the mutant channels however the amount of inactivation of the channels was significantly reduced, still allowing much more Na current through compared to the WT
What is the difference in inactivation in the WT compared to the P2006A mutant
Same rate of inactivation but less channels have inactivated
What effect do all the mutants have on the SCN5A channel
Depolarising shift in Vdep inactivation, require a more positive potential.
All have a faster recovery time from inactivation - time taken to change from inactive to closed state is reduced
What is interesting about the fast inactivating R680H SCN5A mutant
Under normal conditions it doesn’t show a persistent current. However in intracellular acidosis, the current persists due to a loss of inactivation. Becomes important when risk factors also come into play.
