Spatial variability in T-tubule and electrical remodeling of left ventricular epicardium in mouse hearts with transgenic Gαq overexpression-induced pathological hypertrophy.
Spatial variability in T-tubule and electrical remodeling of left ventricular epicardium in mouse hearts with transgenic Gαq overexpression-induced pathological hypertrophy.
复制标题
转基因 Gαq 过度表达诱导的病理性肥大小鼠心脏 T 管的空间变异和左心室心外膜的电重塑。
DOI：
10.1016/j.yjmcc.2012.06.006
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发表时间：
2012
影响因子：
5
通讯作者：
Rubart,Michael
中科院分区：
文献类型：
--
作者：
Tao,Wen;Shi,Jianjian;Dorn2nd,GeraldW;Wei,Lei;Rubart,Michael
病理性左心室肥大（LVH）与心室动作电位延长一致。许多先前的研究，采用各种实验模型的肥大，已经揭示了显着的差异，肥大对动作电位时程（APD）的影响之间的心肌细胞从内膜和心外膜层的LV游离壁。然而，尚不清楚病理性LVH是否也伴随着来自LV游离壁相同层的肌细胞之间APD的重新分布。在这里的实验中，在心脏限制性转基因Gαq过表达产生的失代偿性LVH小鼠模型中检查了LV心外膜动作电位重塑。基于共焦线扫描的光学记录的传播动作电位从个别原位心肌细胞在整个外层的前左心室心外膜表现出空间不均匀的动作电位延长在转基因心脏，引起改变的心外膜复极的空间分散。与野生型心脏相比，Gαq心脏中抗Cx43免疫反应性的局部密度和分布没有变化，表明细胞间偶联保留。共聚焦显微镜还发现在原位心外膜心肌细胞的T-小管的异质性解体。这些数据提供了转基因Gαq过表达诱导肥大心脏的LV心外膜层内存在显著电和结构异质性的证据，并进一步支持了以下观点：一小部分电连接良好的LV组织可以通过控制复极的肌膜离子电流活动的异质性来维持动作电位时程的分散。病理性LVH的其他实验模型，包括压力超负荷LVH，是否同样表现出T-小管组织和/或LV心肌不同层内复极分散的改变，仍有待研究。
Pathological left ventricular hypertrophy (LVH) is consistently associated with prolongation of the ventricular action potentials. A number of previous studies, employing various experimental models of hypertrophy, have revealed marked differences in the effects of hypertrophy on action potential duration (APD) between myocytes from endocardial and epicardial layers of the LV free wall. It is not known, however, whether pathological LVH is also accompanied by redistribution of APD among myocytes from the same layer in the LV free wall. In the experiments here, LV epicardial action potential remodeling was examined in a mouse model of decompensated LVH, produced by cardiac-restricted transgenic Gαq overexpression. Confocal linescanning-based optical recordings of propagated action potentials from individual in situ cardiomyocytes across the outer layer of the anterior LV epicardium demonstrated spatially non-uniform action potential prolongation in transgenic hearts, giving rise to alterations in spatial dispersion of epicardial repolarization. Local density and distribution of anti-Cx43 mmune reactivity in Gαq hearts were unchanged compared to wild-type hearts, suggesting preservation of intercellular coupling. Confocal microscopy also revealed heterogeneous disorganization of T-tubules in epicardial cardiomyocytes in situ. These data provide evidence of the existence of significant electrical and structural heterogeneity within the LV epicardial layer of hearts with transgenic Gαq overexpression-induced hypertrophy, and further support the notion that a small portion of electrically well connected LV tissue can maintain dispersion of action potential duration through heterogeneity in the activities of sarcolemmal ionic currents that control repolarization. It remains to be examined whether other experimental models of pathological LVH, including pressure overload LVH, similarly exhibit alterations in T-tubule organization and/or dispersion of repolarization within distinct layers of LV myocardium.