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The influence of intercalated disk nanostructure on local ionic currents and cardiac conduction
Ruichen Sui1, Nicolae Moise2, Seth H Weinberg2
1Biophysics Graduate Program, The Ohio State University, Columbus, Ohio; Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio.
Biophysical Journal
|November 21, 2025
Summary
The intercalated disk (ID) structure significantly impacts heart function. This study reveals how gap junction coupling and ID nanostructure heterogeneity critically influence cardiac conduction velocity and synchronization.
Area of Science:
- Cardiovascular Research
- Computational Biology
- Biophysics
Background:
- The intercalated disk (ID) is crucial for coordinated heartbeats.
- Existing models often oversimplify ID structure and ion channel distribution, limiting accuracy.
- Nanoscale heterogeneity within the ID is not well understood.
Purpose of the Study:
- To create a more realistic computational model of the intercalated disk.
- To investigate the impact of structural and electrophysiological heterogeneity on cardiac conduction.
- To quantify the relative influence of geometric and nanostructural factors on conduction dynamics.
Main Methods:
- Developed an advanced finite element mesh framework for ID modeling.
- Incorporated spatially heterogeneous gap junctions and multiple ion dynamics.
- Generated 384 ID configurations and simulated tissue-level conduction.
- Utilized neural networks for sensitivity analysis of geometric and nanostructural factors.
Main Results:
- Gap junction coupling, cleft geometry, and nanostructure heterogeneity are key determinants of cleft potential, sodium current synchronization, and conduction velocity.
- Membrane separation in ID regions shows context-dependent effects on conduction.
- Identified regime-dependent roles of ID ultrastructure in cardiac conduction.
Conclusions:
- Established a quantitative framework linking nanoscale ID morphology to tissue-scale cardiac conduction.
- Demonstrated that ID ultrastructure significantly influences cardiac electrophysiology.
- Highlighted the importance of considering nanoscale heterogeneity in cardiac modeling.
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