Conduction abnormality in gap junction protein connexin45-deficient embryonic stem cell-derived cardiac myocytes
Conduction abnormality in gap junction protein connexin45-deficient embryonic stem cell-derived cardiac myocytes
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DOI：
10.1002/ar.a.20110
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发表时间：
2004-10-01
期刊：
影响因子：
--
通讯作者：
Shibata, Y
中科院分区：
文献类型：
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作者：
Egashira, K;Nishii, K;Shibata, Y
在早期心脏，心冲动不通过专门的传导系统传播，而是在心肌细胞之间传播。我们假设间隙连接蛋白connexin45 （Cx45）调节早期心脏收缩，因为它是唯一在早期心脏中描述的间隙连接蛋白。Cx45缺陷（Cx45(-/-)）小鼠死于心力衰竭，并伴有心血管系统的其他复杂缺陷。为了确定Cx45的特异性心肌功能，我们构建了Cx45（-/-）胚胎干（ES）细胞体外分化为心肌。与野生型细胞的协调收缩不同，分化的Cx45（-/-）心肌细胞表现出高且不规则的脉动率。Cx45（-/-）心肌细胞电生理特性的改变是通过平面多电极阵列探针的细胞外记录和荧光Ca2+指示剂fura-2的细胞内Ca2+记录来指示的。体外系统最大限度地减少了使Cx45（-/-）小鼠表型复杂化的血流动力学因素的影响。我们的研究结果表明，Cx45是早期心肌细胞协调传导的重要连接蛋白。本文中提到的补充材料可以在解剖记录网站（http://www.interscience.wiley.com/ jpages/0003-276X/suppmat）上找到。(C) 2004 Wiley-Liss, Inc。
In early-stage heart, the cardiac impulse does not propagate through the specialized conduction system but spreads from myocyte to myocyte. We hypothesized that the gap junction protein connexin45 (Cx45) regulates early-stage contractions, because it is the only gap junction protein described in early hearts. Cx45-deficient (Cx45(-/-)) mice die of heart failure, concomitantly displaying other complex defects in the cardiovascular system. In order to determine the specific cardiac muscular function of Cx45, we created Cx45(-/-) embryonic stem (ES) cells to be differentiated into cardiac muscle in vitro. Unlike the coordinated contractions of wild-type cells, differentiated Cx45(-/-) cardiac myocytes showed high and irregular pulsation rates. Alterations of the electrophysiological properties of the Cx45(-/-) cardiac myocytes were indicated both by extracellular recording on planar multielectrode array probes and by intracellular Ca2+ recording of the fluorescent Ca2+ indicator fura-2. The in vitro system minimizes an influence of hemodynamic factors that complicate the phenotypes of Cx45(-/-) mice. Our results indicate that Cx45 is an essential connexin for coordinated conduction through early cardiac myocytes. The Supplementary Material referred to in this article can be found at the Anatomical Record website (http://www.interscience.wiley.com/ jpages/0003-276X/suppmat). (C) 2004 Wiley-Liss, Inc.