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DY: Fachverband Dynamik und Statistische Physik

DY 51: Focus Session: Nonlinear Dynamics of the Heart II (joint session DY/BP)

DY 51.1: 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 Falcke^{1, 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.