Multiscale Modeling of Dyadic Structure-Function Relation in Ventricular Cardiac Myocytes.
Filippo G Cosi1, Wolfgang Giese2, Wilhelm Neubert2
1Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany; Georg-August-Universität Göttingen, Institute for the Dynamics of Complex Systems, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany.
Biophysical Journal
|October 23, 2019
Summary
This study models cardiac cell defects, finding L-type calcium channel current significantly impacts action potential duration and calcium levels. Ryanodine receptor cluster structure is crucial for cardiac function biomarkers.
Area of Science:
- Cardiovascular Physiology
- Computational Biology
- Cellular Electrophysiology
Background:
- Cardiovascular diseases are linked to cardiac myocyte subcellular defects, particularly in the dyadic cleft.
- Pathological changes in dyadic cleft geometry and channel placement necessitate multiscale modeling approaches.
Purpose of the Study:
- To develop a multiscale model of dyadic structure-function relationships.
- To explore the impact of molecular alterations on cardiac electrophysiology and calcium cycling.
Main Methods:
- Incorporated stochastic simulations of L-type calcium channels and ryanodine receptor channels.
- Utilized spatially detailed concentration dynamics within dyadic clefts.
- Employed rabbit membrane potential dynamics and partial differential equations for cellular calcium handling.
Main Results:
- Action potential duration, systolic, and diastolic calcium concentrations were most sensitive to L-type calcium channel current.
- Ryanodine receptor channel cluster structure significantly affected all investigated biomarkers.
- Cluster shape and channel density (mean occupancy) showed strong correlations with biomarker responses.
Conclusions:
- The multiscale model effectively links molecular changes to whole-cell cardiac function.
- L-type calcium channels and ryanodine receptor cluster organization are critical determinants of cardiac myocyte electrophysiology and calcium handling.
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