Atrial arrhythmogenicity in aged Scn5a+/a†KPQ mice modeling long QT type 3 syndrome and its relationship to Na+ channel expression and cardiac conduction
Atrial arrhythmogenicity in aged Scn5a+/a†KPQ mice modeling long QT type 3 syndrome and its relationship to Na+ channel expression and cardiac conduction
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DOI：
10.1007/s00424-010-0851-z
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发表时间：
2010-08-01
影响因子：
4.5
通讯作者：
Huang, Christopher L. -H.
中科院分区：
文献类型：
--
作者：
Guzadhur, Laila;Pearcey, Sarah M.;Huang, Christopher L. -H.
最近的研究报告，人类Nav1.5突变易患早发性房性心律失常。因此，本实验评估了与心脏Na+通道Nav1.5表达相关的模拟长QT 3综合征的衰老Scn 5a +/a匕首KPQ小鼠中的心房促凝性。使用程序电刺激评估来自3和12月龄野生型（WT）和Scn 5a +/a匕首KPQ小鼠的离体Langendorff灌注心脏中的心房电生理特性，并通过Western印迹评估其Nav1.5表达。在完整麻醉动物中通过心电图评估心脏传导特性。单相动作电位记录显示，老年Scn 5a +/Delta KPQ心脏的心房致心律失常性增加。这些显示出更大的动作电位时程/不应期比值，但心房Nav1.5表达水平低于老年WT小鼠。年轻Scn 5a +/Delta KPQ的心房Nav1.5水平高于年轻WT。WT中这些水平随年龄增加而增加，但Scn 5a +/Delta KPQ中没有。年轻和老年Scn 5a +/Delta KPQ小鼠的心率和PR间期均低于WT小鼠。年轻的Scn 5a +/Delta KPQ小鼠的QT和QTc间期长于年轻的WT。老年Scn 5a +/Delta KPQ显示QRS持续时间长于老年WT。相对于老年WT，年轻WT的PR间期延长，QT间期缩短。相比之下，年轻和老年Scn 5a +/Delta KPQ之间的ECG参数相似。因此，老年鼠Scn 5a +/Delta KPQ心脏表现出增加的心房促心律失常性。Scn 5a +/Delta KPQ和WT之间不同的Nav1.5表达和心脏传导减慢的心电图指标显示出与衰老相关的进一步变化，可能导致老年Scn 5a +/Delta KPQ心脏的房性心律失常。
Recent studies have reported that human mutations in Nav1.5 predispose to early age onset atrial arrhythmia. The present experiments accordingly assess atrial arrhythmogenicity in aging Scn5a+/a dagger KPQ mice modeling long QT3 syndrome in relationship to cardiac Na+ channel, Nav1.5, expression. Atrial electrophysiological properties in isolated Langendorff-perfused hearts from 3- and 12-month-old wild type (WT), and Scn5a+/a dagger KPQ mice were assessed using programmed electrical stimulation and their Nav1.5 expression assessed by Western blot. Cardiac conduction properties were assessed electrocardiographically in intact anesthetized animals. Monophasic action potential recordings demonstrated increased atrial arrhythmogenicity specifically in aged Scn5a+/Delta KPQ hearts. These showed greater action potential duration/refractory period ratios but lower atrial Nav1.5 expression levels than aged WT mice. Atrial Nav1.5 levels were higher in young Scn5a+/Delta KPQ than young WT. These levels increased with age in WT but not Scn5a+/Delta KPQ. Both young and aged Scn5a+/Delta KPQ mice showed lower heart rates and longer PR intervals than their WT counterparts. Young Scn5a+/Delta KPQ mice showed longer QT and QTc intervals than young WT. Aged Scn5a+/Delta KPQ showed longer QRS durations than aged WT. PR intervals were prolonged and QT intervals were shortened in young relative to aged WT. In contrast, ECG parameters were similar between young and aged Scn5a+/Delta KPQ. Aged murine Scn5a+/Delta KPQ hearts thus exhibit an increased atrial arrhythmogenicity. The differing Nav1.5 expression and electrocardiographic indicators of slowed cardiac conduction between Scn5a+/Delta KPQ and WT, which show further variations associated with aging, may contribute toward atrial arrhythmia in aged Scn5a+/Delta KPQ hearts.