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Vol. 65 No. 7: Issue 7

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β-Arrestin2 regulates the rapid component of delayed rectifier K+ currents and cardiac action potential of guinea pig cardiomyocytes after adrenergic stimulation

https://doi.org/10.14715/cmb/2019.65.7.23
Erdan Shi
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
Xiaozhu Zhou
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
Dongcheng Li
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
Yuzhen Zhang
Department of Cardiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China
Jiamin Yuan
Department of Cardiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China
Jiangang Zou
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

Corresponding Author(s) : Erdan Shi

shierdan_njmu@163.com

Cellular and Molecular Biology, Vol. 65 No. 7: Issue 7

Abstract

A decrease in the rapid component of delayed rectifier potassium current (IKr) during chronic heart failure (CHF) prolongs action potential (AP), and plays a key role in the pathogenesis of ventricular arrhythmias. β-Arrestin2 has been shown to restore the inotropic reserve of β-adrenergic regulation, but little or nothing is known about its effect on intrinsic channel. This study investigated the role of β-arrestin2 in the regulation of cardiac hERG/IKr potassium channel and AP during chronic adrenergic stimulation. Single left ventricular myocytes were isolated from guinea pig heart, and were transfected with adenovirus encoding β-arrestin2, or β-arrestin2 siRNA or an empty adenovirus. Cell cultures containing 10 nM isoproterenol, 1 nM phenylephrine or vehicle alone (control medium) were electro-physiologically examined after 48 h of incubation. Action potential duration at 50 and 90 % of repolarization (APD50 and APD90) were measured using whole-cell patch-clamp recording. Sustained adrenergic stimulation significantly reduced the density of the IKr current (p < 0.001). β-Arrestin2 expression in cell cultures treated with isoproterenol or phenylephrine was significantly downregulated after adrenergic stimulation (p < 0.001). Overexpression of β-arrestin2 significantly attenuated isoproterenol or phenylephrine-induced reduction in IKr current. It also prevented the phenylephrine-induced prolongation of AP (p < 0.05 for APD50 and p < 0.001 for APD90), but did not significantly affect AP profile after exposure of the cardiomyocytes to isoproterenol (p > 0.05). Therefore, Increased levels of β-Arrestin2 weaken dysregulation of IKr current and prevent excessive AP prolongation, making it an effective anti-arrhythmic strategy.

Keywords

β-Arrestin2 Adrenergic stimulation Ventricular arrhythmias Action potential Potassium channel.
Shi, E., Zhou, X., Li, D., Zhang, Y., Yuan, J., & Zou, J. (2019). β-Arrestin2 regulates the rapid component of delayed rectifier K+ currents and cardiac action potential of guinea pig cardiomyocytes after adrenergic stimulation. Cellular and Molecular Biology, 65(7), 132–137. https://doi.org/10.14715/cmb/2019.65.7.23
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