CaMKII inhibition reduces isoproterenol-induced ischemia and arrhythmias in hypertrophic mice.
OBJECTIVE
The Ca/calmodulin-dependent protein kinase II (CaMKII), an arrhythmogenic molecule, is excessively activated in cardiac hypertrophy. Here, we investigated the effect of CaMKII inhibition in isoproterenol (ISO)-induced arrhythmias in hypertrophic mice.


RESULTS
ISO induced multiple types of arrhythmias in the hypertrophic mice but not in the normal mice. The QTc intervals were prolonged and the amplitudes of T waves were increased significantly by ISO prior to arrhythmia initiation. Inhibition of CaMKII prevented ISO-induced QTc prolongation and T wave elevation and abrogated arrhythmia induction.


METHODS
Pressure-overload cardiac hypertrophy was induced in mice by thoracic aortic banding. Arrhythmias were recorded by electrocardiogram in conscious mice.


CONCLUSIONS
CaMKII inhibition is effective in suppressing adrenergic activation-induced ventricular arrhythmias in cardiac hypertrophy, of which the ventricular ischemia-induced CaMKII activation plays an important role.
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Ying
Y
Feng
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Jun
J
Cheng
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Baozhu
B
Wei
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.|The Medical Research Institute of Wuhan University, Wuhan, China.
Yanggan
Y
Wang
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000201:enzymology* / Q000209:etiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors*; D006332:Cardiomegaly / Q000150:complications / Q000201:enzymology*; D002316:Cardiotonic Agents / Q000633:toxicity; D004195:Disease Models, Animal; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000201:enzymology
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D007545:Isoproterenol
CaMKII; Pathology Section; adrenergic stimulation; arrhythmia; cardiac hypertrophy