Flashcards in arrythmia stuff Deck (21)
RWD syndrome mutation
1. in the slow cardiac K+ channel IKs (LQT1),
2. the rapid cardiac K+ channel IKr (LQT2)
3. the cardiac Na+ channel INa (LQT3).
JLNS mutations are
homozygous carriers of mutations in IKs (LQT1)
congenital deafness, (homozygous)
while the heterozygous carriers are asymptomatic
the result of reducing the number of K+ channels expressed in the myocyte plasma membrane is?
reduces the size of the K+ current (IKr + IKs) that helps terminate the plateau phase of the fast response and return the membrane to resting potential during diastole.
aka. prolonged plateau
effect of LQT1 mutant slow K+ channels
reduced current amplitude
effect of LQT3 mutant na+ channels
brugada syndrome mutations
1. More than 30 different mutations in the cardiac Na+ channel have been linked to Brugada,
2. with many of these reducing peak inward Na+ current that drives action potential upstroke in ventricular myocytes.
triggered afterdepolarizations: triggered by
Fast response phase 2 is prolonged by
1. ↑ inward current
(incomplete Na+ channel inactivation in LQT3) or by
2. ↓ outward current
(↓ K+ current in LQT1, LQT2).
Ca2+ entry during the prolonged QT interval triggers
(via Ca2+ channel reactivation) or
(via NCX-dependent depolarization).
↑ sympathetic tone (startle) ↑ likelihood of
triggered afterdepolarizations because Ca2+ influx is enhanced by β-adrenergic receptor activity.
heart failure increases the
frequency of occurrence of triggered afterdepolarizations (even without LQT mutations).
Amiodarone is a class
III drug that has, important for its utility, class I action too.
• Class I drugs slow
• Class Ib drugs show
pure class I action: slow upstroke, decreased AP duration
• Class Ia & Class Ic drugs delay
delay phase 3 onset via K+ channel block
Na+ channel block leads to
1. decreased phase 0 upstroke, which leads to
2. decreased conduction velocity, which leads to
3. decreased re entry
All class I:
↓ conduction velocity & ↑refractory period, thereby ↓re-entry
The more frequently a channel is used (activated), the greater the chance that
it will become blocked by the drug.
2. Compared to less active cardiac tissue, over-active cardiac tissue:
“uses” (activates) Na+ channels more, so Na+ channels in over-active tissue will more likely be blocked.