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IK1 channel agonist zacopride suppresses ventricular arrhythmias in conscious rats with healing myocardial infarction.

Authors
  • Zhai, Xuwen1
  • Qiao, Xi2
  • Zhang, Li3
  • Wang, Dongming4
  • Zhang, Lijun2
  • Feng, Qilong5
  • Wu, Bowei5
  • Cao, Jimin6
  • Liu, Qinghua7
  • 1 Clinical Skills Teaching Simulation Hospital, Shanxi Medical University, Taiyuan, China. , (China)
  • 2 Department of Pathophysiology, Shanxi Medical University, Taiyuan, China. , (China)
  • 3 Clinical Laboratory, Children's Hospital of Shanxi, Taiyuan, China. , (China)
  • 4 The Second Hospital of Shanxi Medical University, Taiyuan, China. , (China)
  • 5 Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan 030001, China; Department of Physiology, Shanxi Medical University, Taiyuan 030001, China. , (China)
  • 6 Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan 030001, China; Department of Physiology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: [email protected] , (China)
  • 7 Department of Pathophysiology, Shanxi Medical University, Taiyuan, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Life sciences
Publication Date
Dec 15, 2019
Volume
239
Pages
117075–117075
Identifiers
DOI: 10.1016/j.lfs.2019.117075
PMID: 31751587
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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. IK1/Kir2.1 might be an attractive target for pharmacological controlling of lethal arrhythmias post MI. Copyright © 2019 Elsevier Inc. All rights reserved.

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