Article ; Online: Sodium channel subpopulations with distinct biophysical properties and subcellular localization enhance cardiac conduction.
The Journal of general physiology
2023 Volume 155, Issue 8
Abstract: Sodium (Na+) current is responsible for the rapid depolarization of cardiac myocytes that triggers the cardiac action potential upstroke. Recent studies have illustrated the presence of multiple pools of Na+ channels with distinct biophysical properties ... ...
| Abstract | Sodium (Na+) current is responsible for the rapid depolarization of cardiac myocytes that triggers the cardiac action potential upstroke. Recent studies have illustrated the presence of multiple pools of Na+ channels with distinct biophysical properties and subcellular localization, including clustering of channels at the intercalated disk and along the lateral membrane. Computational studies predict that Na+ channel clusters at the intercalated disk can regulate cardiac conduction via modulation of the narrow intercellular cleft between electrically coupled myocytes. However, these studies have primarily focused on the redistribution of Na+ channels between intercalated disk and lateral membranes and have not considered the distinct biophysical properties of the Na+ channel subpopulations. In this study, we use computational modeling to simulate computational models of single cardiac cells and one-dimensional cardiac tissues and predict the function of distinct Na+ channel subpopulations. Single-cell simulations predict that a subpopulation of Na+ channels with shifted steady-state activation and inactivation voltage dependency promotes an earlier action potential upstroke. In cardiac tissues that account for distinct subcellular spatial localization, simulations predict that shifted Na+ channels contribute to faster and more robust conduction in response to changes in tissue structure (i.e., cleft width), gap junctional coupling, and rapid pacing rates. Simulations predict that the intercalated disk-localized shifted Na+ channels contribute proportionally more to total Na+ charge than lateral membrane-localized Na+ channels. Importantly, our work supports the hypothesis that Na+ channel redistribution may be a critical mechanism by which cells can respond to perturbations to support fast and robust conduction. |
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| MeSH term(s) | Myocardium ; Myocytes, Cardiac/physiology ; Sodium Channels ; Action Potentials/physiology ; Gap Junctions/physiology |
| Chemical Substances | Sodium Channels |
| Language | English |
| Publishing date | 2023-06-07 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 3118-5 |
| ISSN | 1540-7748 ; 0022-1295 |
| ISSN (online) | 1540-7748 |
| ISSN | 0022-1295 |
| DOI | 10.1085/jgp.202313382 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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