Pharmacological enhancement of cardiac gap junction coupling prevents arrhythmias in canine LQT2 model.
Gap junctions contribute to the transmural heterogeneity of repolarization in the normal heart and under conditions of prolonged QT interval in the diseased heart. This study examined whether enhancing of gap junction coupling can reduce transmural dispersion of repolarization (TDR) and prevent torsade de pointes (TdP) in a canine LQT2 model. Canine left ventricular wedge preparations were perfused with delayed rectifier potassium current (IKr) blocker d-sotalol to mimic LQT2 and the antiarrhythmic peptide 10 (AAP10) was used as a gap junction coupling enhancer. As compared with the control group, the LQT2 group had significantly augmented TDR and higher incidence of TdP associated with increased nonphosphorylated connexin 43 (Cx43). AAP10 prevented augmentation of TDR and induction of TdP while rescuing Cx43 phosphorylation. There was no significant change in the quantity and spatial distribution of Cx43. These data indicate that gap junction enhancer AAP10 can prevent augmentation of TDR and suppress TdP by preventing dephosphorylation of Cx43 in a LQT2 model.
Quan
Xiao-Qing
XQ
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Bai
Rong
R
Lu
Jia-Gao
JG
Patel
Chinmay
C
Liu
Nian
N
Ruan
Yanfei
Y
Chen
Bo-Di
BD
Ruan
Lei
L
Zhang
Cun-Tai
CT
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D018031:Connexin 43 / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D022062:Electrophysiologic Techniques, Cardiac; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008133:Long QT Syndrome / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009842:Oligopeptides / Q000494:pharmacology*; D013015:Sotalol / Q000494:pharmacology*; D016171:Torsades de Pointes / Q000517:prevention & control*
C090806:AAP 10; D000889:Anti-Arrhythmia Agents; D018031:Connexin 43; D009842:Oligopeptides; D013015:Sotalol