Characterization of an Extensive Transverse Tubular Network in Sheep Atrial Myocytes and its Depletion in Heart Failure
Characterization of an Extensive Transverse Tubular Network in Sheep Atrial Myocytes and its Depletion in Heart Failure
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DOI：
10.1161/circheartfailure.109.852228
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发表时间：
2009-09-01
影响因子：
9.7
通讯作者：
Trafford, Andrew W.
中科院分区：
文献类型：
--
作者：
Dibb, Katharine M.;Clarke, Jessica D.;Trafford, Andrew W.
背景-在心室肌细胞中，将兴奋与收缩期Ca（2+）升高偶联的大多数结构位于横小管（t-小管）膜。在衰竭的心室中，t-小管的紊乱破坏了兴奋收缩偶联。小哺乳动物的心房中几乎不存在t-小管膜，导致心房和心室细胞在刺激时细胞内Ca（2+）释放的时空特征不同。本研究的目的是确定（一）是否心房肌细胞从一个大型哺乳动物（羊）具有T-小管，（二）这些是否是功能上的重要性，以及（三）是否他们被打乱在heartfault.Methods和Results-Sheep左心房肌细胞用二-4-ANEPPS染色。几乎所有的对照细胞都有一个广泛的t-小管网络，导致细胞中的每个体素比其他情况更接近膜（肌膜或t-小管）。T-小管将50%的体素与膜的距离从3.35 +/- 0.15 μ m减小到0.88 +/- 0.04 μ m。在去极化过程中，细胞内Ca（2+）在细胞周边和中心同时升高。在快速心室起搏引起的心力衰竭中，心房t-小管几乎完全丧失。50%的体素从膜的距离增加到2.04 +/- 0.08 μ m，并有损失的早期Ca（2+）释放从center.Conclusion-Sheep心房肌细胞具有大量的t-微管网络，抑制收缩期Ca（2+）瞬变。在心力衰竭中，这个网络明显中断。这可能在心力衰竭时心房功能改变中起重要作用。(Circ心脏衰竭。2009;2：482-489）。
Background-In ventricular myocytes, the majority of structures that couple excitation to the systolic rise of Ca(2+) are located at the transverse tubular (t-tubule) membrane. In the failing ventricle, disorganization of t-tubules disrupts excitation contraction coupling. The t-tubule membrane is virtually absent in the atria of small mammals resulting in spatiotemporally distinct profiles of intracellular Ca(2+) release on stimulation in atrial and ventricular cells. The aims of this study were to determine (i) whether atrial myocytes from a large mammal (sheep) possess t-tubules, (ii) whether these are functionally important, and (iii) whether they are disrupted in heart failure.Methods and Results-Sheep left atrial myocytes were stained with di-4-ANEPPS. Nearly all control cells had an extensive t-tubule network resulting in each voxel in the cell being nearer to a membrane (sarcolemma or t-tubule) than would otherwise be the case. T-tubules decrease the distance of 50% of voxels from a membrane from 3.35 +/- 0.15 to 0.88 +/- 0.04 mu m. During depolarization, intracellular Ca(2+) rises simultaneously at the cell periphery and center. In heart failure induced by rapid ventricular pacing, there was an almost complete loss of atrial t-tubules. The distance of 50% of voxels from a membrane increased to 2.04 +/- 0.08 mu m, and there was a loss of early Ca(2+) release from the cell center.Conclusion-Sheep atrial myocytes possess a substantial t-tubule network that synchronizes the systolic Ca(2+) transient. In heart failure, this network is markedly disrupted. This may play an important role in changes of atrial function in heart failure. (Circ Heart Fail. 2009;2:482-489.)