Abstract
AimsThe aim of this study was to elucidate the effects of regulator of G-protein signaling 5 (Rgs5), a negative regulator of G protein-mediated signaling, on atrial repolarization and tachyarrhythmia (ATA) in mice.Methods and ResultsIn present study, the incidence of ATA were increased in Rgs5−/− Langendorff-perfused mouse hearts during program electrical stimulation (PES) (46.7%, 7 of 15) and burst pacing (26.7%, 4 of 15) compared with wild-type (WT) mice (PES: 7.1%,1 of 14; burst:7.1%,1 of 14) (P<0.05). And the duration of ATA also shown longer in Rgs5−/− heart than that in WT, 2 out of 15 hearts exhibited sustained ATA (>30 s) but none of them observed in WT mice. Atrial prolonged repolarization was observed in Rgs5−/− hearts including widened P wave in surface ECG recording, increased action potential duration (APD) and atrial effective refractory periods (AERP), all of them showed significant difference with WT mice (P<0.05). At the cellular level, whole-cell patch clamp recorded markedly decreased densities of repolarizing K+ currents including IKur (at +60 mV: 14.0±2.2 pF/pA) and Ito (at +60 mV: 16.7±1.3 pA/pF) in Rgs5−/− atrial cardiomyocytes, compared to those of WT mice (at +60 mV Ito: 20.4±2.0 pA/pF; Ikur: 17.9±2.0 pF/pA) (P<0.05).ConclusionThese results suggest that Rgs5 is an important regulator of arrhythmogenesis in the mouse atrium and that the enhanced susceptibility to atrial tachyarrhythmias in Rgs5−/− mice may contribute to abnormalities of atrial repolarization.
Highlights
Atrial tachyarrhythmia (ATA), characterized by abnormal, disorganized and rapid atrial electrical activity, is a major public health problem
These results suggest that regulator of G-protein signaling 5 (Rgs5) is an important regulator of arrhythmogenesis in the mouse atrium and that the enhanced susceptibility to atrial tachyarrhythmias in Rgs52/2 mice may contribute to abnormalities of atrial repolarization
ECG recording and echocardiography determination To analyze whether Rgs5 deficiency results in atrial electrical abnormalities, telemetry ECG were performed
Summary
Atrial tachyarrhythmia (ATA), characterized by abnormal, disorganized and rapid atrial electrical activity, is a major public health problem. Atrial fibrillation, which affects 0.5% of people over the age of 50 and 10% of people over 80 [2], is a significant burden on health care resources and increases the risk of serious complications including embolic disease, heart failure and sudden cardiac death. Despite the development of diverse animal models and the application of a multitude of pharmacological and non-pharmacological therapies, understanding of the mechanism underlying ATA remained incomplete. The recent discovery of DNA variants associated with ATA provides new insights into the mechanisms underlying arrhythmias. Changes in the expression of multiple genes including KCNQ1, KCNE1 and KCNE2 have been shown predisposed to atrial fibrillation [1,4]. The upstream molecular-regulated targets of pro-arrhythmic substrate need to be better understood
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