Mechanisms Underlying the Formation and Dynamics of Subcellular Calcium Alternans in the Intact Rat Heart
Mechanisms Underlying the Formation and Dynamics of Subcellular Calcium Alternans in the Intact Rat Heart
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DOI：
10.1161/circresaha.108.181909
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发表时间：
2009-03-13
影响因子：
20.1
通讯作者：
Wasserstrom, J. Andrew
中科院分区：
文献类型：
--
作者：
Aistrup, Gary L.;Shiferaw, Yohannes;Wasserstrom, J. Andrew
完整心脏组织的光学测绘表明，在某些情况下，细胞内钙 (Ca) 释放可以按大-小-大顺序从一个心跳交替到下一个心跳，也称为 Ca 瞬时 (CaT) 交替。当细胞的一部分以大-小-大序列交替，而另一部分以小-大-小序列交替时，CaT交替也可能在单个细胞内变得空间相位不匹配，这种现象称为亚细胞不一致交替。这些相位失配模式的形成和时空演化机制尚不清楚。我们使用共聚焦 Ca 成像来测量完整大鼠心脏中单个肌细胞内肌节水平的 CaT 交替。周期长度 (CL) 突然变化后，CaT 交替出现 2 种不同的空间模式。在 CL 变化后的最初几次心跳后，CaT 可以形成空间相位不匹配的交替模式。相位不匹配持续许多节拍，之后通过节点的移动逐渐变得相位匹配，节点是相位不匹配的细胞区域之间的接合处。在其他示例中，通过节点的形成和移动，相位匹配的交替逐渐变得相位不匹配。在这些例子中，我们观察到尽管 CL 起搏恒定，但细胞激活时间的逐搏变化较大。通过计算机模拟，我们探索了这些动态现象的潜在机制。我们的结果表明，肌节水平的异质性与 Ca 循环和膜电压的动力学相结合，如何导致完整心脏的肌细胞内复杂的时空现象。 （Circ Res. 2009；104：639-649。）
Optical mapping of intact cardiac tissue reveals that, in some cases, intracellular calcium (Ca) release can alternate from one beat to the next in a large-small-large sequence, also referred to as Ca transient (CaT) alternans. CaT alternans can also become spatially phase-mismatched within a single cell, when one part of the cell alternates in a large-small-large sequence, whereas a different part alternates in a small-large-small sequence, a phenomenon known as subcellular discordant alternans. The mechanisms for the formation and spatiotemporal evolution of these phase-mismatched patterns are not known. We used confocal Ca imaging to measure CaT alternans at the sarcomeric level within individual myocytes in the intact rat heart. After a sudden change in cycle length (CL), 2 distinct spatial patterns of CaT alternans emerge. CaTs can form spatially phase-mismatched alternans patterns after the first few beats following the change in CL. The phase mismatch persists for many beats, after which it gradually becomes phase matched via the movement of nodes, which are junctures between phase-mismatched cell regions. In other examples, phase-matched alternans gradually become phase-mismatched, via the formation and movement of nodes. In these examples, we observed large beat-to-beat variations in the cell activation times, despite constant CL pacing. Using computer simulations, we explored the underlying mechanisms for these dynamical phenomena. Our results show how heterogeneity at the sarcomeric level, in conjunction with the dynamics of Ca cycling and membrane voltage, can lead to complex spatiotemporal phenomena within myocytes of the intact heart. (Circ Res. 2009; 104: 639-649.)