Antiarrhythmic peptide AAP10 prevents arrhythmias induced by protein kinase C activation in rabbit left ventricular wedges.
As the mechanisms underlying PKC activation induced arrhythmias are not yet fully verified, we investigated the role of gap junctions in arrhythmias induced by PKC activation.Arterially-perfused rabbit left ventricular preparations were randomly assigned to perfusion with phorbol ester (PMA) or in combination with AAP10. Transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded throughout all experiments. Changes in connexin43 (Cx43) and nonphosphorylated Cx43 on S368 were measured by Western blot analysis.In the PMA group, the QT interval was shortened, the interval from the peak to the end of the electrocardiographic T wave (Tp-e) and induced nonsustained ventricular tachycardia (VT) were increased, and the expressions of Cx43 and nonphosphorylated Cx43 on S368 were decreased compared with the control group. Compared with the PMA group, without significant changes in the QT interval and the expression of nonphosphorylated connexin43 on S368, Tp-e and induced VT decreased and the expression of Cx43 increased in the AAP10 group.AAP10 can prevent PMA-induced rabbit ventricular arrhythmias by attenuating the increase of Tp-e and the decrease of expression of Cx43. These data suggest that increasing gap junction coupling prevents arrhythmias induced by protein kinase C activation.
Department of Cardiology, Zhongshan Hospital.
Mingke
M
Ni
Lei
L
Ruan
Cuntai
C
Zhang
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D018031:Connexin 43 / Q000378:metabolism; D004789:Enzyme Activation; D017629:Gap Junctions; D006352:Heart Ventricles; D009842:Oligopeptides / Q000627:therapeutic use*; D010703:Phorbol Esters; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction; D046509:Tissue Culture Techniques
C090806:AAP 10; D018031:Connexin 43; D009842:Oligopeptides; D010703:Phorbol Esters; D011493:Protein Kinase C