SKM 2021 – wissenschaftliches Programm
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DY: Fachverband Dynamik und Statistische Physik
DY 13: Focus session: Nonlinear Dynamics of the Heart II (organized by Markus Bär, Stefan Luther and Ulrich Parlitz)
DY 13.1: Hauptvortrag
Donnerstag, 30. September 2021, 13:30–14:00, H2
Multi-scale modeling of dyadic structure-function relation in ventricular cardiac myocytes — •Martin Falcke1, Filippo G. Cosi2, Wolfgang Giese1, Wilhelm Neubert1, Stefan Luther2, Nagaiah Chmakuri3, and Ulrich Parlitz2 — 1Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany — 2Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany — 3IISER Thiruvananthapuram, India
Cardiovascular disease is often related to defects of sub-cellular 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 multi-scale model to create dyadic structure-function relationships to explore the impact of molecular changes on whole cell electrophysiology and calcium cycling. This multi-scale model incorporates stochastic simulation of individual L-type calcium channels (LCC) and ryanodine receptor channels (RyRs), spatially detailed concentration dynamics in dyadic clefts, rabbit membrane potential dynamics, and a system of partial differential equations for myoplasmic and lumenal free calcium and calcium-binding molecules in the cell bulk. We found action potential duration, systolic and diastolic calcium to respond most sensitive to changes in LCC current. The RyR 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 showed the strongest correlation to the effects on biomarkers.