Mechanical modulation of the transverse tubular system of ventricular cardiomyocytes.

Mechanical modulation of the transverse tubular system of ventricular cardiomyocytes.
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DOI:
10.1016/j.pbiomolbio.2012.07.010
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发表时间:
2012-10
影响因子:
3.8
通讯作者:
Sachse FB
Sachse FB
中科院分区:
生物学3区
文献类型:
--
作者:
McNary TG;Spitzer KW;Holloway H;Bridge JH;Kohl P;Sachse FB

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在大多数哺乳动物心肌细胞中,横管系统(t系统)是电信号和兴奋-收缩偶联的主要场所。T-小管由膜内陷组成,膜内陷由参与兴奋-收缩偶联和机械-电反馈的各种蛋白质装饰。在培养的细胞和各种类型的心脏病中,t系统的重塑已经被报道过。在本文中,我们提供的见解机械应变对兔左心室肌细胞的t-系统的影响。基于荧光标记,三维扫描共聚焦显微镜,和数字图像分析,我们研究了活的和固定的分离细胞在不同的应变条件。我们提取的t-小管的几何特征,其特征在于它们的排列相对于Z-盘。此外,我们研究了t-系统的细胞固定在零左心室压力(松弛),在30毫米汞柱(容量过载),或在锂诱导的挛缩,使用透射电子显微镜。二维图像分析被用来提取特征的t-小管横截面。我们对共聚焦显微镜图像的分析表明,细胞水平的挛缩导致t系统变形,增加t小管的长度和体积,并改变其横截面形状。TEM数据再次证实了机械诱导的T管横截面的变化的存在。总之,我们的研究表明,被动纵向拉伸和主动收缩的心室心肌细胞影响的几何形状的t-小管。这证实了细胞水平的机械变化可以促进部分体积的改变,这将支持t系统内容物和细胞外空间之间的对流辅助模式的交换。
In most mammalian cardiomyocytes, the transverse tubular system (t-system) is a major site for electrical signaling and excitation-contraction coupling. T-tubules consist of membrane invaginations, which are decorated with various proteins involved in excitation-contraction coupling and mechano-electric feedback. Remodeling of the t-system has been reported for cells in culture and various types of heart disease. In this paper, we provide insights into effects of mechanical strain on the t-system in rabbit left ventricular myocytes. Based on fluorescent labeling, three-dimensional scanning confocal microscopy, and digital image analysis, we studied living and fixed isolated cells in different strain conditions. We extracted geometric features of t-tubules and characterized their arrangement with respect to the Z-disk. In addition, we studied the t-system in cells from hearts fixed either at zero left ventricular pressure (slack), at 30 mmHg (volume overload), or during lithium-induced contracture, using transmission electron microscopy. Two-dimensional image analysis was used to extract features of t-tubule cross-sections. Our analyses of confocal microscopic images showed that contracture at the cellular level causes deformation of the t-system, increasing the length and volume of t-tubules, and altering their cross-sectional shape. TEM data reconfirmed the presence of mechanically induced changes in T-tubular cross sections. In summary, our studies suggest that passive longitudinal stretching and active contraction of ventricular cardiomyocytes affect the geometry of t-tubules. This confirms that mechanical changes at cellular levels could promote alterations in partial volumes that would support a convection-assisted mode of exchange between the t-system content and extracellular space.
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