Abstract 188: Atrial Tachyarrhythmia in Rgs5-Null Mice

Abstract

Abstract Aims The 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 Results In present study, the incidence of ATA were increased in isolated mouse Rgs5^-/- 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^{[[Unable to Display Character: +]]/-} heart than that in WT, 2 out of 15 hearts exhibited sustained ATA (>30s) 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 increased densities of repolarizing K⁺ currents including I_Kur (at + 60mV: 14.0 ± 2.2 pF/pA) and I_to (at + 60mV: 16.7±1.3 pA/pF) in Rgs5^-/- atrial cardiomyocytes, compared to those of WT mice (at + 60mV I_to: 20.4 ± 2.0 pA/pF; I_kur: 17.9 ± 2.0 pF/pA) (P<0.05).

Conclusion These 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.