Flashcards in arrhythmia mechanism 2 Deck (21):
antiarrhythmic drugs should be selected based on the
specific molecular basis of long QT syndrome.
For patients with the LQT3 mutations, use:
drugs that block Na+ channels
for patients with LQT1 or LQT2 mutations, use:
drugs that open K+ channels ought to be used
effects of Ina
incomplete Ina inactiation
effects of Ica-L
incomplete Ica inactivation
autism (timothy syndrome)
effects of Ikr
decrease in K+ current
effects of Iks
decrease in K+ current
effects of Ik1
decrease in K+ current (during diastole)
1. congenital arrythmia
2. ventricular fibrillation results in a survival rate of only 40% by 5 years of age.
finnish familial arrhythmia mechanism
1, The protein yotiao binds protein kinase A, cardiac Ca2+ channels and K+ channels Yotiao thus anchors this kinase to cardiac Ca2+ and IKS channels
2. A mutation in IKS channels prevents yotiao binding to this channel
3. The mutant K+ is not properly upregulated by β receptor activity
In finnish familial arrythmia, yotiao mutation leads to
1. during ↑ sympathetic activity (exercise, emotion),
2. not enough repolarizing K+ current to match the increased depolarizing Ca2+ current.
3. Phase 2 is prolonged, cytosolic Ca2+ levels rise, triggering afterdepolarizations and arrhythmia.
two types of problems in arrhythmia:
(1) inappropriate impulse initiation in SA node or elsewhere (ectopic focus), and
(2) disturbed impulse conduction in nodes, conduction cells (Purkinje cells) or myocytes.
Inappropriate impulse initiation - identified by
abnormally depolarized diastolic membrane potential
Inappropriate impulse initiation - caused by
1. ectopic foci
2. triggered afterdepolarizations
because normal SA nodal pacemaker is abnormally slow, or ectopic focus is abnormally fast infarct - causes membrane to depolarize
(decrease in [K+]i occurs as Na/K-ATPase fails)
early afterdepolarizations (EADs):
1. appear during late phase 2 and phase 3
2. largely dependent upon re-activation of Ca2+ channels in response to elevated [Ca2+]in prolongation of phase 2 (long QT) contributes to elevated [Ca2+]in
delayed afterdepolarizations (DADs):
1. during early phase 4
2. initiated by elevated [Ca2+]in and, consequently, elevated Na+/Ca2+ exchange
3. the Na+/Ca2+ exchanger is electrogenic: 3 Na+ move in for 1 Ca2+ moved out
4. net increase in positive charge inside myocytes corresponds to depolarization this exchanger is called NCX, and the current it generates is INCX
Prolonged phase 2
INCX will cause
excess Ca2+ entry, which triggers excess Ca2+ release from SR.
Elevated [Ca2+]in drives increased Na/Ca exchange via the NCX exchanger.
Prolongation of QT interval leads to
early afterdepolarizations and arrhythmia.
Disturbed impulse conduction: Will cause:
1. conduction block