Severe Cardiovascular Disease
Effect of KN93 on delayed afterdepolarization and calcium ion in ventricular myocytes of rabbits with heart failure
Jun Ke, Yang Li, Feng Chen, Chao Zhu, Xiaoping Wang, Bendun Chen, Shifeng Li, Zheng Gong
Published 2018-10-10
Cite as Chin J Emerg Med, 2018, 27(10): 1089-1094. DOI: 10.3760/cma.j.issn.1671-0282.2018.10.005
Abstract
ObjectiveTo observe the effect of KN93, a CaMKⅡ inhibitor, on delayed afterdepolarization (DAD) and calcium ion in ventricular myocytes of rabbits with heart failure, and to investigate the effect of CaMKⅡ signaling pathway on trigged arrhythmia after heart failure.
MethodsThirty male New Zealand White rabbits were randomized(random number) into the sham operated group (sham group), heart failure group (HF group) and heart failure with KN93 group (HF+KN93 group) (n=10 each group). The rabbit heart failure model was established by abdominal aortic constriction combined with aortic valve regurgitation. The ventricular myocytes were isolated by double enzyme digestion. The action potential and the transient inward current (Iti) were recorded by the whole-cell patch-clamp. The intracellular calcium transient was measured by the ion concentration measurement system. The main calcium transporter protein was detected by Western blotting. Data were analyzed by pCLAMP10.2. Statistical analysis was performed using SPSS 17.0. Comparisons among groups were conducted using ANOVA, and SNK-q multiple comparison procedure was utilized for post-hoc analysis.
Results(1) After induction of heart failure, DAD and increment of trigger activity (TA) were observed in rabbit ventricular myocytes. Treatment of KN93 with 1.0 μmol/L reduced the events of DAD and TA. (2) After induction of heart failure, Iti densities were increased from -0.12±0.02 pA/pF to -0.95±0.06 pA/pF at the polarization potential of -50 mV (n=10, P<0.01). The current densities were reduced to -0.44±0.04 pA/pF after application of 1.0 μmol/L of KN93 (n=10, P<0.01). (3) KN93 led to decrement of intracellular calcium ion concentration and calcium transient amplitude, and acceleration of the decay process of calcium transient. (4) KN93 upregulated the expression of pPLN and SERCA2a, increased the uptake of intracellular calcium ion, downregulated the expression of NCX, decreased the Iti, and reduced the occurrence of DAD and TA.
ConclusionsKN93 can reduce the intracellular calcium ion concentration of the heart failure animal model, and the occurrence of the DAD and TA. CaMKⅡ may be a new therapeutic target for arrhythmias in the heart failure.
Key words:
KN93; Heart failure; Delayed afterdepolarization; Transient inward current; Calcium ion
Contributor Information
Jun Ke
Emergency Department, Fujian Provincial Hospital, Provincial College of Clinical Medicine, Fujian Medical University, Fujian Emergency Medical Center, Fujian Provincial Institute of Emergency Medicine, Fuzhou 350001, China
Yang Li
Cardiology Department, General Hospital of People’s Liberation Army, Beijing 100853, China
Feng Chen
Emergency Department, Fujian Provincial Hospital, Provincial College of Clinical Medicine, Fujian Medical University, Fujian Emergency Medical Center, Fujian Provincial Institute of Emergency Medicine, Fuzhou 350001, China
Chao Zhu
Cardiology Department, General Hospital of People’s Liberation Army, Beijing 100853, China
Xiaoping Wang
Emergency Department, Fujian Provincial Hospital, Provincial College of Clinical Medicine, Fujian Medical University, Fujian Emergency Medical Center, Fujian Provincial Institute of Emergency Medicine, Fuzhou 350001, China
Bendun Chen
Emergency Department, Fujian Provincial Hospital, Provincial College of Clinical Medicine, Fujian Medical University, Fujian Emergency Medical Center, Fujian Provincial Institute of Emergency Medicine, Fuzhou 350001, China
Shifeng Li
Emergency Department, Fujian Provincial Hospital, Provincial College of Clinical Medicine, Fujian Medical University, Fujian Emergency Medical Center, Fujian Provincial Institute of Emergency Medicine, Fuzhou 350001, China
Zheng Gong
Emergency Department, Fujian Provincial Hospital, Provincial College of Clinical Medicine, Fujian Medical University, Fujian Emergency Medical Center, Fujian Provincial Institute of Emergency Medicine, Fuzhou 350001, China
