Atrial tachyarrhythmia in Rgs5-null mice.

Atrial tachyarrhythmia in Rgs5-null mice.
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Rgs5 缺失小鼠的房性快速心律失常

DOI:
10.1371/journal.pone.0046856
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Huang C
Huang C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Qin M;Huang H;Wang T;Hu H;Liu Y;Gu Y;Cao H;Li H;Huang C

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目的探讨G蛋白信号负调控因子Rgs 5对小鼠心房复极和快速性心律失常的影响。方法与结果Rgs 5 −/− Langendorff灌流小鼠心脏程序电刺激(PES)和短阵起搏(burst pacing)时ATA发生率分别为46.7%(7/15)和26.7%(4/15),与野生型(WT)小鼠相比(PES:7.1%,1/14; burst:7.1%,1/14),差异有统计学意义(P<0.05)。Rgs 5-/-小鼠心脏ATA持续时间也较WT小鼠长,15只小鼠中有2只出现持续性ATA(>30 s),而WT小鼠无一例出现。Rgs 5-/-小鼠心房复极延长,体表心电图P波增宽,动作电位时程(APD)延长,心房有效不应期(AERP)延长,与WT小鼠比较差异有统计学意义(P<0.05)。在细胞水平,全细胞膜片钳记录到明显降低的复极化钾电流密度,包括IKur(+60 mV时:14.0±2.2 pF/pA)和Ito(+60 mV时:16.7±1.3 pA/pF),与WT小鼠相比Ito为20.4±2.0 pA/pF,Ikur为17.9±2.0 pF/pA(P<0.05)。结论Rgs 5是小鼠心房肌发生的重要调节因子,Rgs 5 −/−小鼠对房性快速心律失常的易感性增强可能与心房复极异常有关。
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 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). 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.
DOI: 10.1093/cvr/cvn020
发表时间: 2008-04-01
影响因子: 10.8
作者:
Rivard, Katy;Paradis, Pierre;Fiset, Celine
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影响因子: 6.1
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发表时间: 2007-08-01
影响因子: 4.8
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通讯作者: Schirdewan, Alexander