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08 October 2014 : Original article  

Pioglitazone Improves Potassium Channel Remodeling Induced by Angiotensin II in Atrial Myocytes

Jun GuBEF, Wei HuADG, Xu LiuACDG

DOI: 10.12659/MSMBR.892450

Med Sci Monit Basic Res 2014; 20:153-160

Abstract

BACKGROUND: It has been demonstrated that atrial electrical remodeling contributes toward atrial fibrillation (AF) maintenance, and that angiotensin II (AngII) is involved in the pathogenesis of atrial electrical remodeling. Peroxisome proliferator activated receptor-γ (PPAR-γ) agonists have been shown to inhibit atrial electrical remodeling, but the underlying mechanisms are poorly understood. In the present study we investigated the regulating effects of PPAR-g agonist on AngII-induced potassium channel remodeling in atrial myocytes.

MATERIAL AND METHODS: Whole-cell patch-clamp technique was used to record transient outward potassium current (Ito), ultra-rapid delayed rectifier potassium (Ikur), and inward rectifier potassium current (Ik1). Real-time PCR was used to assess potassium channel subunit mRNA expression.

RESULTS: Compared with the control group, AngII reduced Ito and Ikur current density as well as amplified Ik1 current density, which were partially prevented by pioglitazone. Furthermore, pioglitazone alleviated the downregulation of Ito subunit (Kv 4.2) and Ikur subunit (Kv 1.5), as well as the upregulation of Ik1 subunit (Kir 2.1 and Kir 2.2) mRNA expression stimulated by AngII.

CONCLUSIONS: These results suggest that pioglitazone exhibits a beneficial effect on AngII-induced potassium channel remodeling. PPAR-γ agonists may be potentially effective up-stream therapies for AF.

Keywords: Atrial Remodeling - drug effects, Angiotensin II - pharmacology, Cell Line, Electrophysiological Phenomena - drug effects, Gene Expression Regulation - drug effects, Heart Atria - cytology, Ion Channel Gating - drug effects, Myocytes, Cardiac - physiology, Potassium Channels - metabolism, RNA, Messenger - metabolism, Real-Time Polymerase Chain Reaction, Thiazolidinediones - pharmacology

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416