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Multiscale modeling of dyadic structure-function relation in ventricular cardiac myocytes

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Item Type:Article
Title:Multiscale modeling of dyadic structure-function relation in ventricular cardiac myocytes
Creators Name:Cosi, F.G. and Giese, W. and Neubert, W. and Luther, S. and Chamakuri, N. and Parlitz, U. and Falcke, M.
Abstract:Cardiovascular disease is often related to defects of subcellular components in cardiac myocytes, specifically in the dyadic cleft, which include changes in cleft geometry and channel placement. Modeling of these pathological changes requires both spatially resolved cleft as well as whole cell level descriptions. We use a multiscale model to create dyadic structure-function relationships to explore the impact of molecular changes on whole cell electrophysiology and calcium cycling. This multiscale model incorporates stochastic simulation of individual L-type calcium channels and ryanodine receptor channels, spatially detailed concentration dynamics in dyadic clefts, rabbit membrane potential dynamics, and a system of partial differential equations for myoplasmic and lumenal free Ca(2+) and Ca(2+)-binding molecules in the bulk of the cell. We found action potential duration, systolic, and diastolic [Ca(2+)] to respond most sensitively to changes in L-type calcium channel current. The ryanodine receptor channel cluster structure inside dyadic clefts was found to affect all biomarkers investigated. The shape of clusters observed in experiments by Jayasinghe et al. and channel density within the cluster (characterized by mean occupancy) showed the strongest correlation to the effects on biomarkers.
Keywords:Action Potentials, Cardiac Myocytes, Cardiovascular Models, Heart Ventricles, Ryanodine Receptor Calcium Release Channel, Sarcoplasmic Reticulum
Source:Biophysical Journal
Publisher:Cell Press
Page Range:2409-2419
Date:17 December 2019
Official Publication:https://doi.org/10.1016/j.bpj.2019.09.023
PubMed:View item in PubMed

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