Atrial Tachyarrhythmia in Rgs5-Null Mice

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 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 I(Kur) (at +60 mV: 14.0±2.2 pF/pA) and I(to) (at +60 mV: 16.7±1.3 pA/pF) in Rgs5(-/-) atrial cardiomyocytes, compared to those of WT mice (at +60 mV 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.