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BP: Fachverband Biologische Physik
BP 34: Nonlinear Dynamics of the Heart II (joint session DY/BP)
BP 34.1: Hauptvortrag
Donnerstag, 19. März 2020, 14:00–14:30, ZEU 118
Dyadic structure-function relationships in ventricular cardiac myocytes: from sparks to action potentials — •Martin Falcke1, 2, Filippo G. Cosi3, Wolfgang Giese1, Wilhelm Neubert1, Stefan Luther3, and Ulrich Parlitz3 — 1Max Delbrück Center, Berlin — 2Dept. of Physics, Humboldt University Berlin — 3MPI for Dynamics and Self-Organization, Göttingen
Cardiovascular disease is often related to defects in molecular and sub-cellular components in cardiac myocytes, specifically in the dyadic cleft, which include changes in cleft geometry and channel placement. Modelling of these pathological changes requires both spatially resolved cleft as well as the whole cell level descriptions. We use a multiscale model to create dyadic structure-function relationships in order 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 (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 Ca2+ and Ca2+-binding molecules in the bulk of the cell.
We create models with varying dyadic cleft properties including RyR and LCC clustering, stochastic opening and closing rates as well as changes in LCC and RyR calcium currents. We investigate biomarkers describing action potential, Ca2+ transient and Ca2+ spark dynamics. We quantify sensitivity and parameter uncertainty and derive cellular functional implications from molecular level properties.