Pioglitazone improves potassium channel remodeling induced by angiotensin II in atrial myocytes.
Pioglitazone improves potassium channel remodeling induced by angiotensin II in atrial myocytes.
复制标题
DOI：
10.12659/msmbr.892450
复制
发表时间：
2014-10-08
影响因子：
2.8
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Gu J;Hu W;Liu X
心房电重构是心房颤动（AF）的重要机制之一，血管紧张素II（AngII）参与了心房电重构的发生。过氧化物酶体增殖物激活受体-γ（Peroxisome proliferator activated receptor-γ，PPAR-γ）激动剂可抑制心房电重构，但其作用机制尚不清楚。本研究探讨了PPAR-γ激动剂对血管紧张素Ⅱ（AngII）诱导的心房肌细胞钾通道重构的调节作用。采用全细胞膜片钳技术记录瞬时外向钾电流（Ito）、超快速延迟整流钾电流（Ikur）和内向整流钾电流（Ik 1）。实时荧光定量PCR检测钾通道亚基mRNA表达。与对照组相比，AngII降低Ito和Ikur电流密度，放大Ik 1电流密度，吡格列酮可部分阻止AngII降低Ito和Ikur电流密度，放大Ik 1电流密度。此外，吡格列酮还能减轻AngII诱导的Ito亚基（Kv 4.2）和Ikur亚基（Kv 1.5）的下调以及Ik 1亚基（Kir 2.1和Kir 2.2）mRNA表达的上调。这些结果表明，吡格列酮对AngII诱导的钾通道重塑具有有益作用。PPAR-γ激动剂可能是治疗房颤的有效上游药物。
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-γ agonist on AngII-induced potassium channel remodeling in atrial myocytes. 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. 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. 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.