Modelling the Structure and Function of Cardiac Cell Transverse-Axial-Tubules

Abstract

Modelling the Structure and Function of Transverse-Axial-TubulesThe past decades have seen significant strides being made in understanding the structure and function of the heart using experimental and computational approaches. Mathematical models of the heart can now represent the anatomical structure of the whole-heart and simulate the heart beat using biophysically based methods on the computer. At the cellular-level, however, mathematical models typically simulate the function using black-box mass kinetics approaches and make several simplifying assumptions regarding the spatial scale and organization of the key cellular components in excitation-contraction coupling. While these studies have been pivotal in gaining quantitative insights on cardiac cell activity, a deeper understanding of structure function relationships at the cellular scale can only be gained by incorporating more realistic models of the geometry. With this aim, we present an anatomically realistic finite element model of the cardiac cell sarcolemma, and its transverse-axial tubule system. Confocal microscopy images of the sarcolemma and t-tubules of an isolated wistar rat myocyte were acquired, segmented and skeletonized. A two-dimensional surface mesh was fitted to the sarcolemma data, and one-dimensional finite elements were used to represent the t-tubules from the skeletonized image in three-dimensional space. This representation will form the basis to simulate calcium diffusion into the cell cytosol during the excitation phase of excitation-contraction coupling. We present preliminary results from these simulations, and provide first quantitative insights into cardiac cell excitation in 3D.