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扭曲的心脏闰盘调节电突触耦合。

Tortuous Cardiac Intercalated Discs Modulate Ephaptic Coupling.

机构信息

Department of Physiology, University of Bern, CH-3012 Bern, Switzerland.

出版信息

Cells. 2022 Nov 2;11(21):3477. doi: 10.3390/cells11213477.

DOI:10.3390/cells11213477
PMID:36359872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9655400/
Abstract

Cardiac ephaptic coupling, a mechanism mediated by negative electric potentials occurring in the narrow intercellular clefts of intercalated discs, can influence action potential propagation by modulating the sodium current. Intercalated discs are highly tortuous due to the mingling of plicate and interplicate regions. To investigate the effect of their convoluted structure on ephaptic coupling, we refined our previous model of an intercalated disc and tested predefined folded geometries, which we parametrized by orientation, amplitude and number of folds. Ephaptic interactions (assessed by the minimal cleft potential and amplitude of the sodium currents) were reinforced by concentric folds. With increasing amplitude and number of concentric folds, the cleft potential became more negative during the sodium current transient. This is explained by the larger resistance between the cleft and the bulk extracellular space. In contrast, radial folds attenuated ephaptic interactions and led to a less negative cleft potential due to a decreased net cleft resistance. In conclusion, despite limitations inherent to the simplified geometries and sodium channel distributions investigated as well as simplifications regarding ion concentration changes, these results indicate that the folding pattern of intercalated discs modulates ephaptic coupling.

摘要

心脏电突触偶联是一种通过在闰盘的狭窄细胞间隙中产生负电潜力来介导的机制,它可以通过调节钠电流来影响动作电位的传播。闰盘由于褶皱和平行区域的混合而高度扭曲。为了研究其复杂结构对电突触偶联的影响,我们改进了以前的闰盘模型,并测试了预定义的折叠几何形状,我们通过取向、幅度和折叠数量对其进行了参数化。电突触相互作用(通过最小的缝隙电位和钠电流的幅度来评估)被同心折叠增强。随着同心折叠幅度和数量的增加,钠电流瞬变过程中的缝隙电位变得更负。这是由于缝隙和胞外空间的电阻较大所致。相比之下,径向折叠减弱了电突触相互作用,导致缝隙电位变得不那么负,这是由于净缝隙电阻减小所致。总之,尽管受到所研究的简化几何形状和钠通道分布以及离子浓度变化的简化的限制,这些结果表明闰盘的折叠模式调节了电突触偶联。

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Localization of Na channel clusters in narrowed perinexi of gap junctions enhances cardiac impulse transmission via ephaptic coupling: a model study.缝隙连接变窄处的钠通道簇定位增强了电突触耦合的心脏冲动传递:一项模型研究。
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2
Intercalated disk nanoscale structure regulates cardiac conduction.闰盘纳米结构调节心脏传导。
J Gen Physiol. 2021 Aug 2;153(8). doi: 10.1085/jgp.202112897. Epub 2021 Jul 15.
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Vascular endothelial growth factor promotes atrial arrhythmias by inducing acute intercalated disk remodeling.
具有不同生物物理特性和亚细胞定位的钠通道亚群增强心脏传导。
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Nano-scale solution of the Poisson-Nernst-Planck (PNP) equations in a fraction of two neighboring cells reveals the magnitude of intercellular electrochemical waves.纳诺尺度下泊松-纳诺-普朗克(PNP)方程在两个相邻细胞的分数中的解揭示了细胞间电化学波的幅度。
PLoS Comput Biol. 2023 Feb 15;19(2):e1010895. doi: 10.1371/journal.pcbi.1010895. eCollection 2023 Feb.
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Sci Rep. 2020 Nov 24;10(1):20463. doi: 10.1038/s41598-020-77562-5.
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