Tortuous Cardiac Intercalated Discs Modulate Ephaptic Coupling

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

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.

Keywords: cardiac electrophysiology; computer modeling; ephaptic coupling; intercalated discs; sodium channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Heart*
  • Myocardium* / metabolism
  • Sodium / metabolism
  • Sodium Channels

Substances

  • Sodium
  • Sodium Channels

Grants and funding

This work was supported by the Swiss National Science Foundation (grant no. 310030_184707 to J.P.K.).