Ex vivo, microelectrode analysis of conduction through the AV node of wild-type and Nkx2-5 mutant mouse hearts as guided by a Cx40-eGFP transgenic reporter.
Ex vivo, microelectrode analysis of conduction through the AV node of wild-type and Nkx2-5 mutant mouse hearts as guided by a Cx40-eGFP transgenic reporter.
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DOI：
10.14814/phy2.285
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发表时间：
2014
影响因子：
2.5
通讯作者：
Jay PY
中科院分区：
文献类型：
--
作者：
Gazit AZ;Li A;Choi JS;Miquerol L;Jay PY
心脏转录因子NKX 2 - 5的突变导致房室结发育不良和传导阻滞。变异房室结的解剖结构与其功能的关系尚不清楚。因此，我们在野生型和Nkx 2 - 5+/−小鼠心脏的离体制备物中研究了通过AV结区域的传导，其中转基因Cx40-eGFP报告基因突出显示了中枢传导系统。荧光成像引导的房室结下入路和上级入路的电极放置和起搏。与野生型相比，Nkx 2 - 5+/-心脏具有延长的心房-希氏间期，与先前的体内观察结果一致。Nkx 2 - 5+/−心脏从Cx40+下结上级和紧邻Cx40+下结的Cx40− AV结区域到His束的传导时间略长于野生型心脏，但不显著长于野生型心脏。还观察到一种新的表型。在刺激强度增加的情况下，起搏房室结的Cx40−下入路导致野生型心脏而非Nkx 2 - 5+/−心脏的刺激-希氏传导间期进行性缩短。在两组中，Cx40−上级入路的起搏强度对传导间期没有影响。Nkx 2 - 5+/−心脏的AV延迟延长似乎出现在Cx40+下结之前。起搏表型是否解释了突变体的传导缺陷尚不确定，但观察结果增加了房室结下入路的一些独特性质。心脏转录因子NKX 2 - 5的突变导致房室结发育不全和相关传导缺陷。在这里，我们使用微电极来测量心房心肌中的位置与房室结和希氏束的子域之间的传导间期，由Cx40‐eGFP荧光成像引导。我们还报告了起搏房室结下入路的新特性及其相关突变表型。
Mutations of the cardiac transcription factor NKX2‐5 cause hypoplastic development of the AV node and conduction block. How the anatomy of the mutant AV node relates to its function is unknown. We thus studied conduction through the AV nodal region in ex vivo preparations of wild‐type and Nkx2‐5+/− mouse hearts in which the central conduction system was highlighted by a transgenic Cx40‐eGFP reporter. Fluorescence imaging guided electrode placement and pacing of the inferior and superior approaches to the AV node. Nkx2‐5+/− hearts had a prolonged atrio‐His interval compared to the wild type, consistent with previous in vivo observations. The conduction time to the His bundle from the Cx40− AV nodal region that is superior to and immediately adjacent to the Cx40+ lower node is slightly, but not significantly greater in Nkx2‐5+/− than wild‐type hearts. A novel phenotype was also observed. Pacing the Cx40− inferior approach to the AV node with increasing stimulus strength led to progressive shortening of the stimulus‐to‐His conduction interval in wild‐type but not Nkx2‐5+/− hearts. The strength of pacing at the Cx40− superior approach had no effect on the conduction interval in either group. The prolonged AV delay in the Nkx2‐5+/− heart appears to arise before the Cx40+ lower node. Whether the pacing phenotype explains the mutant's conduction defect is uncertain, but the observation adds to a number of unique properties of the inferior approach to the AV node. Mutations of the cardiac transcription factor NKX2‐5 cause hypoplastic development of the AV node and associated conduction defects. Here, we use microelectrodes to measure conduction intervals between locations in the atrial myocardium and subdomains of the AV node and the His bundle, as guided by Cx40‐eGFP fluorescence imaging. We also report a novel property of pacing the inferior approach to the AV node and its related mutant phenotype.