Basic / Cellular EP Flashcards
Mutations in what ion channel cause LQT type II
Ikr (KCNH2, HERG)
Mutations in IKr gene cause what type of LQTS
LQT Type II
Mutations in the IKs gene cause what type of LQTS
LQT Type I
Mutations in what ion channel cause LQT Type I
Iks
All QT prolonging drugs delay current in which ion channel?
Ikr (KNCH2, HERG)
Mutations in what ion channel cause LQT type I
Iks (coded for by KCNQ1 & minK (kvLQT1) & KCNE1
There are 3 delayed rectifiers in the human heart. What are they
Ikur (ultra rapid), Ikr (rapid) and Iks (slow)
Which delayed rectifier is found only in atrial tissue
Ikur
Which type of after depolarization is blunted by an increase in heartbeat?
Early after depolarization
Torsades de pointe is usually triggered by what kind of triggered activity?
Early after depolarization
Which type of triggered activity is cause by a net inward phase III current?
Early after depolarization
Overdose of what drug is associated with delayed after depolarization?
Digoxin
Which type of after depolarization is caused by inappropriate calcium handling?
Delayed after depolarization
What is the conduction velocity in healthy myocardium?
0.6 - 0.7 m/s (from Kyoko Soejima’s N+1 paper published in JACC 2001).
How is bidirectional VT like ping-pong?
During slow rate no triggered activity. As heart rate increases - the right bundle activates the RV (DAD) and subsequently the LV retrograde. The left bundle sees sinus activation and the activation from the DAD on the right, which causes a triggered beat that will activate the RV. Alex A. Baher & James N. Weiss HRS 2014
In humans, what part of the myocardium is most sensitive to the effects of ischemia during VF? How does that impact the clinical rx of a VF cardiac arrest?
In humans (in contrast to pigs), the epicardium is much more vulnerable to the effects of ischemia. The effect of this is that in late VF the epicardium becomes unexcitable and thus a shock may not work. Reperfusion with chest compressions may “reactivate” areas of the epicardium and allow defibrillation to be successful.
In the context of VF, what are “mother rotors”
This concept challenges the idea that VF is random varying loops of ventricular activation but instead can be the consequence of a dominant rotor of electrical activity.
How might myofibroblasts be important in arrhythmogenesis?
According to a study in heart rhythm 2009 by Stephan Rohr, Myofibroblasts are capable of passive conduction across the distance of 300 µm. This observation might explain slow conduction through The anastomosis in a transplanted heart, for example. It also may explain the conduction across a surgical scar in the maze procedure.
Initial attempts at creating a biologic pacemaker focused on overexpression of individual ion channels in working myocardium. What were the drawbacks of this approach and what is the current (in 2013) approaches to creating a biological pacemaker)
Initial constructs involving overexpression of specific ion channels tended to have problems with proarrhythmia. More recent efforts have focused on transcription factors TBX3 & TBX18. These seem to regulate multiple gene expression downstream. Dobrzynski H 2013 - review article
What are some of the hurdles that stem cell therapy must overcome before it can be implemented as common clinical therapy?
- rejection and the need for immunosuppression, 2. a better understanding of malignant potential, 3. long term sustainability of the cells or their effect
How are the SA and AV nodes anatomically and functionally similar?
- Both have transition zones with hybid cellular properties between working myocardium and nodal tissue
- Both are Ca+ dependent action potentials
- Both have iKf and normal automaticity
- Both demonstrate slow conduction due to a paucity of gap junctions (low Cx43 expression)
The conduction velocity of normal working myocardium is 0.6-0.7 m/s. What is the conduction velocity of the His-Purkinje system?
2.3 m/s - more than 3x the speed!
Name 3 reasons for the increased conduction velocity of the H-P system compared to normal myocardium
- large and medium conductance connexins (Cx40 and Cx43 rather than small conductance Cx45)
- Rapid AP upstroke
- longer duration APs
Name 3 cellular electrophysiologic properties of Purkinje fibers that promote arrhythmia
- long action potential duration contributes to torsades de pointes
- PF’s long action potentials are prone to DAD’s which can trigger VT
- PF’s have 2 stable resting potential, one near−90 mVand one near−50 mV. These different states have different conduction properties which can promote bundle branch reentry.
Halina Dobrzynski - Pharmacology & Therapeutics 139 (2013) 260–288
