Voltage-mediated mechanism for calcium wave synchronization and arrhythmogenesis in atrial tissue
Voltage-mediated mechanism for calcium wave synchronization and arrhythmogenesis in atrial tissue
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DOI：
10.1016/j.bpj.2021.12.040
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发表时间：
2022-02-01
影响因子：
3.4
通讯作者：
Shiferaw, Yohannes
中科院分区：
文献类型：
--
作者：
Greene, D'Artagnan;Kaboudian, Abouzar;Shiferaw, Yohannes
调节钙（Ca）循环的蛋白质的分子缺陷引起了广泛的心房心律失常。在许多情况下，这些缺陷促进了细胞中亚细胞Ca波的传播，这会扰乱电压时程并引起动作电位（AP）的危险扰动。然而，亚细胞Ca波在细胞中随机发生，因此，细胞之间的电耦合大大降低了它们对AP的影响。在这项研究中，我们提出的证据表明，心房组织中的钙波可以同步的相位由于有序-无序相变。特别是，我们表明，低于一个临界起搏速率，钙波去极化，因此不会引起大量的AP波动组织。然而，超过这个临界起搏速率，Ca波在数百万个细胞上逐渐同步，这导致AP波动的急剧放大。我们利用潜在的伊辛对称性起搏心脏组织表明，这种过渡表现出普遍的性质共同的广泛的物理系统的性质。最后，我们表明，在心脏中，相位同步诱导空间异相AP持续时间交替驱动波破碎和折返。这些结果表明，心脏组织表现出相变，这是所需的亚细胞钙循环缺陷，以诱导危及生命的心律失常。
A wide range of atrial arrythmias are caused by molecular defects in proteins that regulate calcium (Ca) cycling. In many cases, these defects promote the propagation of subcellular Ca waves in the cell, which can perturb the voltage time course and induce dangerous perturbations of the action potential (AP). However, subcellular Ca waves occur randomly in cells and, therefore, electrical coupling between cells substantially decreases their effect on the AP. In this study, we present evidence that Ca waves in atrial tissue can synchronize in-phase owing to an order-disorder phase transition. In particular, we show that, below a critical pacing rate, Ca waves are desynchronized and therefore do not induce substantial AP fluctuations in tissue. However, above this critical pacing rate, Ca waves gradually synchronize over millions of cells, which leads to a dramatic amplification of AP fluctuations. We exploit an underlying Ising symmetry of paced cardiac tissue to show that this transition exhibits universal properties common to a wide range of physical systems in nature. Finally, we show that in the heart, phase synchronization induces spatially out-of-phase AP duration alternans which drives wave break and reentry. These results suggest that cardiac tissue exhibits a phase transition that is required for subcellular Ca cycling defects to induce a life-threatening arrhythmia.