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

Cosi, F. G., Giese, W., Neubert, W., Luther, S., Chamakuri, N., Parlitz, U., et al. (2019). Multiscale modeling of dyadic structure-function relation in ventricular cardiac myocytes. Biophysical Journal, 117(12), 2409-2419. doi:10.1016/j.bpj.2019.09.023.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-4871-B Version Permalink: http://hdl.handle.net/21.11116/0000-0005-6F26-5
Genre: Journal Article

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 Creators:
Cosi, F. G., Author
Giese, W., Author
Neubert, W., Author
Luther, Stefan1, Author              
Chamakuri, N., Author
Parlitz, Ulrich1, Author              
Falcke, M., Author
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1Research Group Biomedical Physics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society, ou_2063288              

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 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 Ca2+ and Ca2+-binding molecules in the bulk of the cell. We found action potential duration, systolic, and diastolic [Ca2+] 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.

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Language(s): eng - English
 Dates: 2019-09-232019-12-17
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.bpj.2019.09.023
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Title: Biophysical Journal
Source Genre: Journal
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Pages: - Volume / Issue: 117 (12) Sequence Number: - Start / End Page: 2409 - 2419 Identifier: -