Title : ( Constitutively Active Acetylcholine-Dependent Potassium Current Increases Atrial Defibrillation Threshold by Favoring Post-Shock Re-Initiation )
Authors: B. O. Bingen , Saïd F. A. Askar , Zeinab Neshati , Iolanda Feola , A. V. Panfilov , A. A. F. de Vries , Daniël A. Pijnappels ,
Full TextAbstract
Electrical cardioversion (ECV), a mainstay in atrial fibrillation (AF) treatment, is unsuccessful in up to 10–20% of patients. An important aspect of the remodeling process caused by AF is the constitutive activition of the atrium-specific acetylcholine-dependent potassium current (IK,ACh → IK,ACh-c), which is associated with ECV failure. This study investigated the role of IK,ACh-c in ECV failure and setting the atrial defibrillation threshold (aDFT) in optically mapped neonatal rat cardiomyocyte monolayers. AF was induced by burst pacing followed by application of biphasic shocks of 25–100 V to determine aDFT. Blocking IK,ACh-c by tertiapin significantly decreased DFT, which correlated with a significant increase in wavelength during reentry. Genetic knockdown experiments, using lentiviral vectors encoding a Kcnj5-specific shRNA to modulate IK,ACh-c, yielded similar results. Mechanistically, failed ECV was attributed to incomplete phase singularity (PS) removal or reemergence of PSs (i.e. reinitiation) through unidirectional propagation of shock-induced action potentials. Re-initiation occurred at significantly higher voltages than incomplete PS-removal and was inhibited by IK,ACh-c blockade. Whole-heart mapping confirmed our findings showing a 60% increase in ECV success rate after IK,ACh-c blockade. This study provides new mechanistic insight into failing ECV of AF and identifies IK,ACh-c as possible atrium-specific target to increase ECV effectiveness, while decreasing its harmfulness.
Keywords
, Potassium Current, Atrial Defibrillation, Post-Shock Re-Initiation
@article{paperid:1060986,
author = {B. O. Bingen and Saïd F. A. Askar and Neshati, Zeinab and Iolanda Feola and A. V. Panfilov and A. A. F. De Vries and Daniël A. Pijnappels},
title = {Constitutively Active Acetylcholine-Dependent Potassium Current Increases Atrial Defibrillation Threshold by Favoring Post-Shock Re-Initiation},
journal = {Scientific Reports},
year = {2015},
volume = {5},
number = {15187},
month = {October},
issn = {2045-2322},
pages = {1--15},
numpages = {14},
keywords = {Potassium Current; Atrial Defibrillation;Post-Shock Re-Initiation},
}
%0 Journal Article
%T Constitutively Active Acetylcholine-Dependent Potassium Current Increases Atrial Defibrillation Threshold by Favoring Post-Shock Re-Initiation
%A B. O. Bingen
%A Saïd F. A. Askar
%A Neshati, Zeinab
%A Iolanda Feola
%A A. V. Panfilov
%A A. A. F. De Vries
%A Daniël A. Pijnappels
%J Scientific Reports
%@ 2045-2322
%D 2015
