IK1 channel agonist zacopride suppresses ventricular arrhythmias in conscious rats with healing myocardial infarction
| Autor: | Li-Jun Zhang, Li Zhang, Qing-Hua Liu, Qi-Long Feng, Bo-Wei Wu, Dong-Ming Wang, Xu-Wen Zhai, Jimin Cao, Xi Qiao |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Agonist medicine.medical_specialty medicine.drug_class Ventricular tachycardia 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Zacopride 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Ca2+/calmodulin-dependent protein kinase medicine cardiovascular diseases Myocardial infarction General Pharmacology Toxicology and Pharmaceutics Cardioprotection business.industry General Medicine medicine.disease 030104 developmental biology medicine.anatomical_structure chemistry Ventricle Ventricular fibrillation cardiovascular system Cardiology business |
| Zdroj: | Life Sciences. 239:117075 |
| ISSN: | 0024-3205 |
| Popis: | Aims Arrhythmogenesis of chronic myocardial infarction (MI) is associated with the prolongation of action potential, reduction of inward rectifier potassium (IK1, Kir) channels and hyper-activity of Calcium/calmodulin-dependent kinase II (CaMKII) in cardiomyocytes. Zacopride, a selective IK1 agonist, was applied to clarify the cardioprotection of IK1 agonism via a CaMKII signaling on arrhythmias post-MI. Methods Male SD rats were implanted wireless transmitter in the abdominal cavity and subjected to left main coronary artery ligation or sham operation. The telemetric ECGs were monitored per day throughout 4 weeks. At the endpoint, isoproterenol (1.28 mg/kg, i.v.) was administered for provocation test. The expressions of Kir2.1 (dominant subunit of IK1 in ventricle) and CaMKII were detected by Western-blotting. Key findings In the telemetric rats post-MI, zacopride significantly reduced the episodes of atrioventricular conduction block (AVB), premature ventricular contraction (PVC), ventricular tachycardia (VT) and ventricular fibrillation (VF), without significant effect on superventricular premature contraction (SPVC). In provocation test, zacopride suppressed the onset of ventricular arrhythmias in conscious PMI or sham rats. The expression of Kir2.1 was significantly downregulated and p-CaMKII was upregulated post-MI, whereas both were restored by zacopride treatment. Significance IK1/Kir2.1 might be an attractive target for pharmacological controlling of lethal arrhythmias post MI. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect