Scn3b knockout mice exhibit abnormal sino-atrial and cardiac conduction properties.
Scn3b knockout mice exhibit abnormal sino-atrial and cardiac conduction properties.
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DOI：
10.1111/j.1748-1716.2009.02048.x
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Huang CL
中科院分区：
文献类型：
--
作者：
Hakim P;Brice N;Thresher R;Lawrence J;Zhang Y;Jackson AP;Grace AA;Huang CL
与Nav1.5 α-亚基作用的广泛报道相反，很少有研究将β-亚基与心脏血管发生联系起来。我们研究了Scn 3b −/−小鼠心脏的窦房和传导特性。在野生型（WT）和Scn 3b −/−小鼠的心脏中比较了以下特性：（1）心房组织中Scn 3b、Scn 1b和Scn 5a的mRNA表达水平。(2)心肌细胞β3蛋白的表达(3)完整麻醉制剂中的心电图记录。(4)自发搏动和电刺激Langendorff灌注心脏心房的双极电描记图记录。野生型心脏的心房表达Scn 3b mRNA，但Scn 3b −/−心脏不表达。这与Scn 1b和Scn 5a mRNA的相似表达水平相反。免疫荧光实验证实，β3蛋白在WT中表达，而在Scn 3b −/−心肌细胞中不表达。Scn 3b −/−小鼠的I导联心电图显示心率较慢，P波持续时间较长，PR间期较WT心脏延长。自发搏动的Langendorff灌注的Scn 3b −/−心脏表现出异常的心房电生理特性和心房和心室活动部分或完全分离的证据。心房短阵起搏方案在所有Scn 3b −/−心脏中诱导了房性心动过速和房颤，但几乎没有WT心脏。Scn 3b-/-心脏还表现出比WT心脏显着更长的窦房结恢复时间。这些研究结果表明，第一次，在Scn 3b的缺乏导致显着的心房电生理和心内传导异常，补充了心室电生理学的变化在较早的场合报道。
In contrast to extensive reports on the roles of Nav1.5 α-subunits, there have been few studies associating the β-subunits with cardiac arrhythmogenesis. We investigated the sino-atrial and conduction properties in the hearts of Scn3b−/− mice. The following properties were compared in the hearts of wild-type (WT) and Scn3b−/− mice: (1) mRNA expression levels of Scn3b, Scn1b and Scn5a in atrial tissue. (2) Expression of the β3 protein in isolated cardiac myocytes. (3) Electrocardiographic recordings in intact anaesthetized preparations. (4) Bipolar electrogram recordings from the atria of spontaneously beating and electrically stimulated Langendorff-perfused hearts. Scn3b mRNA was expressed in the atria of WT but not Scn3b−/− hearts. This was in contrast to similar expression levels of Scn1b and Scn5a mRNA. Immunofluorescence experiments confirmed that the β3 protein was expressed in WT and absent in Scn3b−/− cardiac myocytes. Lead I electrocardiograms from Scn3b−/− mice showed slower heart rates, longer P wave durations and prolonged PR intervals than WT hearts. Spontaneously beating Langendorff-perfused Scn3b−/− hearts demonstrated both abnormal atrial electrophysiological properties and evidence of partial or complete dissociation of atrial and ventricular activity. Atrial burst pacing protocols induced atrial tachycardia and fibrillation in all Scn3b−/− but hardly any WT hearts. Scn3b−/− hearts also demonstrated significantly longer sinus node recovery times than WT hearts. These findings demonstrate, for the first time, that a deficiency in Scn3b results in significant atrial electrophysiological and intracardiac conduction abnormalities, complementing the changes in ventricular electrophysiology reported on an earlier occasion.
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影响因子：
4.4
作者：
MAKITA, N;SLOANBROWN, K;GEORGE, AL
通讯作者：
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影响因子：
120.7
作者：
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影响因子：
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作者：
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