Role of ephaptic coupling in discordant alternans domain sizes and action potential propagation in the heart.
Role of ephaptic coupling in discordant alternans domain sizes and action potential propagation in the heart.
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DOI：
10.1103/physreve.107.054407
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发表时间：
2023-05
影响因子：
2.4
通讯作者：
Weinberg, Seth H.
中科院分区：
文献类型：
--
作者：
Otani, Niels F.;Figueroa, Eileen;Garrison, James;Hewson, Michelle;Munoz, Laura;Fenton, Flavio H.;Karma, Alain;Weinberg, Seth H.
不一致交替，即心脏中传播动作电位的持续时间的空间异相交替，已与纤维性颤动（一种主要的心脏节律紊乱）的发作相关联。这些交替在其中同步的区域或域的大小在这个链接中是至关重要的。然而，采用细胞之间基于标准间隙连接的耦合的计算机模型已无法同时再现实验中所见的小域尺寸和快速动作电位传播速度。在这里，我们使用计算方法表明，快速的波速和小域的大小是可能的，当一个更详细的模型，考虑到所谓的ephaptic效应的细胞间耦合。我们提供的证据表明，更小的域的大小是可能的，因为不同的耦合强度可以存在于波前上，这两个ephaptic和间隙结耦合参与，在相反的波背，只有间隙结耦合起着积极的作用。耦合强度的差异是由于高密度的快速向内（钠）通道，已知定位在心脏细胞的末端，这是唯一活跃的（从而从事ephaptic耦合）在波前传播。因此，我们的研究结果表明，这种快速向内通道的分布，以及其他因素负责的关键参与ephaptic耦合波传播，包括细胞间的裂缝间距，在增加心脏的脆弱性，危及生命的快速性心律失常发挥重要作用。我们的研究结果，结合在标准的间隙连接为主的耦合模型中的短波长不一致交替域的情况下，也提供了证据，间隙连接和ephaptic耦合是至关重要的波前传播和波回动力学。
Discordant alternans, the spatially out-of-phase alternation of the durations of propagating action potentials in the heart, has been linked to the onset of fibrillation, a major cardiac rhythm disorder. The sizes of the regions, or domains, within which these alternations are synchronized are critical in this link. However, computer models employing standard gap junction-based coupling between cells have been unable to reproduce simultaneously the small domain sizes and rapid action potential propagation speeds seen in experiments. Here we use computational methods to show that rapid wave speeds and small domain sizes are possible when a more detailed model of intercellular coupling that accounts for so-called ephaptic effects is used. We provide evidence that the smaller domain sizes are possible, because different coupling strengths can exist on the wavefronts, for which both ephaptic and gap-junction coupling are involved, in contrast to the wavebacks, where only gap-junction coupling plays an active role. The differences in coupling strength are due to the high density of fast-inward (sodium) channels known to localize on the ends of cardiac cells, which are only active (and thus engage ephaptic coupling) during wavefront propagation. Thus, our results suggest that this distribution of fast-inward channels, as well as other factors responsible for the critical involvement of ephaptic coupling in wave propagation, including intercellular cleft spacing, play important roles in increasing the vulnerability of the heart to life-threatening tachyarrhythmias. Our results, combined with the absence of short-wavelength discordant alternans domains in standard gap-junction-dominated coupling models, also provide evidence that both gap-junction and ephaptic coupling are critical in wavefront propagation and waveback dynamics.
DOI：
10.1016/j.hroo.2021.06.008
发表时间：
2021-08
期刊：
Heart rhythm O2
影响因子：
--
作者：
Uzelac I;Kaboudian A;Iravanian S;Siles-Paredes JG;Gumbart JC;Ashikaga H;Bhatia N;Gilmour RF Jr;Cherry EM;Fenton FH
通讯作者：
Fenton FH
影响因子：
3.7
作者：
Sato D;Bers DM;Shiferaw Y
通讯作者：
Shiferaw Y