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Glycogen synthase kinase 3 beta inhibitor SB216763 improves Kir2.1 expression after myocardia infraction in rats
Cheng Chang1, Shu-Hui Wang1, Li-Na Xu1
1Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.
Background:
Abnormal ion channel currents caused by myocardial electrical remodeling is one of the main causes of malignant arrhythmias. Glycogen synthase kinase 3β (GSK-3β) is the main therapeutic target following ischemia as it regulates nerve cell channels. However, few studies have investigated its role in myocardial electrical remodeling. The present study aimed to investigate the role of GSK-3β in a rat myocardial infarction (MI)-induced electrical remodeling and potential effects on cardiac ionic channels including KCNJ2/Kir2.1/IK1.
Methods:
Ligation of the left anterior descending artery in rats was performed to establish a MI model. The rats were randomly divided into three groups, the sham, MI, and MI + SB group. The animals in the latter group were administered SB216763 (GSK-3β inhibitor) at a dose of 0.6 mg·kg-1·day-1. The ventricular function was assessed by echocardiography, electrocardiography, and histological analysis 7 days post-surgery. Serum was collected to measure lactate dehydrogenase and cardiac troponin I levels, and the mRNA and protein levels of the KCNJ2/Kir2.1/IK1 channel in the heart tissues were assessed. H9c2 cells were cultured to examine the effects of SB216763 on the protein expression of Kir2.1 channel under hypoxic conditions.
Results:
The results revealed that SB216763 ameliorated acute cardiac injury and improved myocardial dysfunction. Moreover, SB216763 increased the mRNA and protein expression of Kir2.1 during MI. Furthermore, SB216763 treatment abrogated the decreased expression of Kir2.1 in H9c2 cells under hypoxic conditions.
Conclusions:
GSK-3β inhibition upregulates Kir2.1 expression in a rat model of MI.
Insights
Inhibition of glycogen synthase kinase 3β (GSK-3β) improves cardiac function after myocardial infarction (MI) in rats. This treatment upregulates the Kir2.1 channel, a key factor in preventing arrhythmias.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Abnormal ion channel currents in myocardial electrical remodeling contribute to malignant arrhythmias.
- Glycogen synthase kinase 3β (GSK-3β) is a therapeutic target for ischemia, regulating nerve cell channels.
- The role of GSK-3β in myocardial electrical remodeling and its impact on cardiac ionic channels remain underexplored.
Purpose of the Study:
- To investigate the role of GSK-3β in myocardial infarction (MI)-induced electrical remodeling in rats.
- To examine the effects of GSK-3β inhibition on cardiac ionic channels, specifically KCNJ2/Kir2.1/IK1.
Main Methods:
- A rat model of MI was established via left anterior descending artery ligation.
- Rats were treated with SB216763 (a GSK-3β inhibitor) or a placebo.
- Ventricular function, cardiac injury markers, and KCNJ2/Kir2.1/IK1 mRNA and protein levels were assessed. H9c2 cells were used to study Kir2.1 expression under hypoxia.
Main Results:
- SB216763 treatment ameliorated acute cardiac injury and improved myocardial dysfunction in the MI model.
- GSK-3β inhibition increased both mRNA and protein expression of Kir2.1 during MI.
- SB216763 reversed the hypoxia-induced decrease in Kir2.1 protein expression in H9c2 cells.
Conclusions:
- GSK-3β inhibition upregulates Kir2.1 expression in a rat model of myocardial infarction.
- Targeting GSK-3β may represent a novel therapeutic strategy for managing arrhythmias associated with MI.
