Heterogeneous expression of gap junction channels in the heart leads to conduction defects and ventricular dysfunction
Heterogeneous expression of gap junction channels in the heart leads to conduction defects and ventricular dysfunction
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DOI：
10.1161/hc3601.093990
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发表时间：
2001-09-04
期刊：
影响因子：
37.8
通讯作者：
Fishman, GI
中科院分区：
文献类型：
--
作者：
Gutstein, DE;Morley, GE;Fishman, GI
背景-在许多心脏病中观察到缝隙连接的异质性重构。随后的同步心室激动丧失被假设为导致心脏性能下降。为了直接测试这一假设，我们设计了一个小鼠模型的异质性间隙连接通道expression.Methods和结果，我们产生嵌合小鼠形成的连接蛋白43（Cx43）缺陷的胚胎干细胞和野生型或基因标记的ROSA 26受体囊胚。嵌合小鼠发育正常，没有心肌纤维化或肥大的组织学证据。Cx43的异质性表达导致传导缺陷，然而，以及显着抑制收缩功能。用电压敏感染料对嵌合体心脏进行光学标测，发现心外膜传导模式高度不规则，量化为激活波阵面的负曲率显著增大（嵌合体小鼠为-1.86+/-0.40 mm，对照组为-0.86+/-0.098 mm; P
Background-Heterogeneous remodeling of gap junctions is observed in many forms of heart disease. The consequent loss of synchronous ventricular activation has been hypothesized to result in diminished cardiac performance. To directly test this hypothesis, we designed a murine model of heterogeneous gap junction channel expression.Methods and Results-We generated chimeric mice formed from connexin43 (Cx43)-deficient embryonic stein cells and wild-type or genetically marked ROSA26 recipient blastocysts. Chimeric mice developed normally, without histological evidence of myocardial fibrosis or hypertrophy. Heterogeneous Cx43 expression resulted in conduction defects, however, as well as markedly depressed contractile function. Optical mapping of chimeric hearts by use of voltage-sensitive dyes revealed highly irregular epicardial conduction patterns, quantified as significantly greater negative curvature of the activation wave front (-1.86+/-0.40 mm in chimeric mice versus -0.86+/-0.098 mm. in controls; P