4.6 Article

Tortuous Cardiac Intercalated Discs Modulate Ephaptic Coupling

期刊

CELLS
卷 11, 期 21, 页码 -

出版社

MDPI
DOI: 10.3390/cells11213477

关键词

cardiac electrophysiology; intercalated discs; ephaptic coupling; sodium channels; computer modeling

资金

  1. Swiss National Science Foundation [310030_184707]
  2. Swiss National Science Foundation (SNF) [310030_184707] Funding Source: Swiss National Science Foundation (SNF)

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Cardiac ephaptic coupling, mediated by negative electric potentials in intercalated discs, can be influenced by the convoluted structure of the discs. Concentric folds enhance ephaptic interactions, while radial folds attenuate ephaptic interactions.
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.

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