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Pioglitazone improves potassium channel remodeling induced by angiotensin II in atrial myocytes.

Gu J, Hu W, Liu X - Med Sci Monit Basic Res (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Shanghai Minhang District Central Hospital, Fudan University, Shanghai, China (mainland).

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/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.

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Related in: MedlinePlus

Effect of pioglitazone on AngII inducing current-voltage (I–V) curve change of Ito in HL-1 cells. Quiescent HL-1 cells were pretreated with pioglitazone (10 μM) or vehicle for 60 min then stimulated with 1 μM AngII for 24 h. (A) Representative recordings of whole-cell Ito are shown for the control, AngII, and AngII+pioglitazone. (B) Ito current density-voltage (I–V) curve in control, AngII, and AngII+pioglitazone. Data represent means ±SD of 5 independent experiments.
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f1-medscimonitbasicres-20-153: Effect of pioglitazone on AngII inducing current-voltage (I–V) curve change of Ito in HL-1 cells. Quiescent HL-1 cells were pretreated with pioglitazone (10 μM) or vehicle for 60 min then stimulated with 1 μM AngII for 24 h. (A) Representative recordings of whole-cell Ito are shown for the control, AngII, and AngII+pioglitazone. (B) Ito current density-voltage (I–V) curve in control, AngII, and AngII+pioglitazone. Data represent means ±SD of 5 independent experiments.

Mentions: Figure 1 shows AngII (1 μM) reduced the peak of Ito current density from 6.3±0.6 pA/pF to 3.6±0.4 pA/pF (P<0.01) at 50 mV compared with the control group, but the addition of pioglitazone (10 μM) markedly alleviated this change (4.8±1.0 pA/pF vs. 3.6±0.4 pA/pF, P<0.05). Furthermore, AngII made the I–V curve shift downward compared with the control group, but preincubation with pioglitazone partially prevented AngII-induced alteration.


Pioglitazone improves potassium channel remodeling induced by angiotensin II in atrial myocytes.

Gu J, Hu W, Liu X - Med Sci Monit Basic Res (2014)

Effect of pioglitazone on AngII inducing current-voltage (I–V) curve change of Ito in HL-1 cells. Quiescent HL-1 cells were pretreated with pioglitazone (10 μM) or vehicle for 60 min then stimulated with 1 μM AngII for 24 h. (A) Representative recordings of whole-cell Ito are shown for the control, AngII, and AngII+pioglitazone. (B) Ito current density-voltage (I–V) curve in control, AngII, and AngII+pioglitazone. Data represent means ±SD of 5 independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4206483&req=5

f1-medscimonitbasicres-20-153: Effect of pioglitazone on AngII inducing current-voltage (I–V) curve change of Ito in HL-1 cells. Quiescent HL-1 cells were pretreated with pioglitazone (10 μM) or vehicle for 60 min then stimulated with 1 μM AngII for 24 h. (A) Representative recordings of whole-cell Ito are shown for the control, AngII, and AngII+pioglitazone. (B) Ito current density-voltage (I–V) curve in control, AngII, and AngII+pioglitazone. Data represent means ±SD of 5 independent experiments.
Mentions: Figure 1 shows AngII (1 μM) reduced the peak of Ito current density from 6.3±0.6 pA/pF to 3.6±0.4 pA/pF (P<0.01) at 50 mV compared with the control group, but the addition of pioglitazone (10 μM) markedly alleviated this change (4.8±1.0 pA/pF vs. 3.6±0.4 pA/pF, P<0.05). Furthermore, AngII made the I–V curve shift downward compared with the control group, but preincubation with pioglitazone partially prevented AngII-induced alteration.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Shanghai Minhang District Central Hospital, Fudan University, Shanghai, China (mainland).

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/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.

Show MeSH
Related in: MedlinePlus