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- W3217492761 abstract "The intercalated disk (ID) is a specialized subcellular region that provides electrical and mechanical connections between myocytes in the heart. The ID has a clearly defined passive role in cardiac tissue, transmitting mechanical forces and electrical currents between cells. Recent studies have shown that Na+ channels, the primary current responsible for cardiac excitation, are preferentially localized at the ID, particularly within nanodomains such as the gap junction-adjacent perinexus and mechanical junction-associated adhesion-excitability nodes, and that perturbations of ID structure, such as those that appear in disease states like heart failure or atrial fibrillation, alter cardiac conduction. This suggests that the ID may play an important, active role in regulating conduction. However, no systematic investigation of how ID nanostructure influences cardiac conduction in health or disease has yet been done. Based on our previously published work, we develop an approach to integrate the distribution of ion channels within the ID and ID nanoscale structure in a realistic finite element model, based on experimental measurements from transmission electron microscopy (TEM) and stochastic optical reconstruction microscopy (STORM) images. Tissue-scale simulations demonstrated that ID structural heterogeneity leads to significant spatial variation in electrical polarization within the intercellular cleft. Importantly, we find that this heterogeneous cleft polarization regulates conduction by desynchronizing the activation of post-junctional Na+ currents. Further, we find that disruption of local ID nanodomains can lead to either conduction slowing or enhancing, depending on gap junctional coupling strength. Overall, our study demonstrates that ID nanoscale structure and ion channel distribution can play a significant role in regulating cardiac conduction." @default.
- W3217492761 created "2021-12-06" @default.
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- W3217492761 date "2021-11-16" @default.
- W3217492761 modified "2023-10-17" @default.
- W3217492761 title "Abstract 13429: Intercalated Disk Nanoscale Structure and Ion Channel Distribution Regulate Cardiac Conduction" @default.
- W3217492761 doi "https://doi.org/10.1161/circ.144.suppl_1.13429" @default.
- W3217492761 hasPublicationYear "2021" @default.
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