Absence of Rgs5 Influences the Spatial and Temporal Fluctuation of Cardiac Repolarization in Mice.

Zi-Liang Song,Yang Liu,Xu Liu,Mu Qin

doi:10.3389/fphys.2021.622084

Abstract

AimsThis study investigated the contribution of the regulator of G-protein signaling 5 (Rgs5) knockout to the alteration of the action potential duration (APD) restitution and repolarizing dispersion in ventricle.Methods and ResultsThe effects of Rgs5–/– were investigated by QT variance (QTv) and heart rate variability analysis of Rgs5–/– mice. Monophasic action potential analysis was investigated in isolated Rgs5–/– heart. Rgs5–/– did not promote ventricular remodeling. The 24-h QTv and QT variability index (QTVI) of the Rgs5–/– mice were higher than those of wild-type (WT) mice (P < 0.01). In WT mice, a positive correlation was found between QTv and the standard deviation of all NN intervals (r = 0.62; P < 0.01), but not in Rgs5–/– mice (R = 0.01; P > 0.05). The absence of Rgs5 resulted in a significant prolongation of effective refractory period and APD in isolated ventricle. In addition, compared with WT mice, the knockout of Rgs5 significantly deepened the slope of the APD recovery curve at all 10 sites of the heart (P < 0.01) and increased the spatial dispersions of Smax (COV-Smax) (WT: 0.28 ± 0.03, Rgs5–/–: 0.53 ± 0.08, P < 0.01). Compared with WT heart, Rgs5–/– increased the induced S1–S2 interval at all sites of heart and widened the window of vulnerability of ventricular tachyarrhythmia (P < 0.05).ConclusionOur findings indicate that Rgs5–/– is an important regulator of ventricular tachyarrhythmia in mice by prolonging ventricular repolarization and increasing spatial dispersion in ventricle.

Highlights

The regulator of G-protein signaling 5 (Rgs5) negatively regulates G-protein-coupled-receptormediated signaling by accelerating the activity of GTPase and dissociation of GTP-bound Gα subunit (Zhou et al, 2001)
Echocardiography was applied to confirm whether the electrical alterations were associated with ventricular dilation, which showed that by measuring fractional shortening (FS) and left ventricular ejection fraction (EF), Rgs5−/− mice did not exhibit ventricular dysfunction (Table 1)
The major findings are as follows: (1) Rgs5−/− prolonged ventricular repolarization and increased spatial heterogeneity of repolarization; (2) Rgs5−/− steepened action potential duration (APD) restitution curves and increased spatial dispersion among ventricle; (3) ventricular tachyarrhythmia was facilitated by Rgs5−/−; and (4) Rgs5−/− induced ventricular arrhythmia (VA), which was not dependent on myocardial fibrosis

Summary

Introduction

The regulator of G-protein signaling 5 (Rgs5) negatively regulates G-protein-coupled-receptormediated signaling by accelerating the activity of GTPase and dissociation of GTP-bound Gα subunit (Zhou et al, 2001). Our previous study showed that knockout of Rgs prolonged cardiac repolarization through reconstructing voltage-dependent K+ currents (Qin et al, 2012), but the electrophysiological mechanisms of arrhythmogenesis need to be better understood. The mechanism of ventricular repolarization leading to spatial heterogeneity is mainly related to. Rgs5−/− Influences Cardiac Repolarization different distributions of ion channels (Antzelevitch, 2007), and genesis of temporal fluctuation was associated with sympathetic tone (Myles et al, 2008; Hinterseer et al, 2010). The method of analyzing beatto-beat QT variability has enabled investigators to determine the prognosis of temporal fluctuation of ventricular repolarization (Dobson et al, 2013)

Methods

Results

Discussion

Conclusion