Title: 3D Model of Synchronous Calcium Signals in Ventricular Myocyte

Abstract: Synchronized calcium signaling (SCS) is characterized by high gradient near the t-tubule membrane and low gradient in the cytoplasm in the transverse direction, which enables ventricular myocyte to respond rapidly and forcefully to electrical and chemical stimuli. We developed a 3D continuum model to investigate the role of structural and functional cellular components in regulating SCS. The model currently includes: 3D geometry of a single t-tubule and its surrounding half-sarcomeres; spatially distributed L-type calcium channel (LCC), sodium calcium exchanger and calcium pump; calcium entry and extrusion across the sarcolemma membrane; and calcium diffusion and buffering by ATP, fluo-3 and troponin C. To solve the reaction diffusion system, the finite element method in space was used in combination with the finite difference method in time. Results suggest that both t-tubule structure and the spatially heterogeneous distribution of calcium handling proteins are important for SCS. The model predicts that two aspects of heterogeneous distribution are required: the concentration of calcium handling proteins in the t-tubule membrane to be ~6 times of that in the surface membrane; and the concentration of LCC, in the cytoplasmic end of the t-tubule, to be ~2.3 times of that in the surface membrane end. These results suggest that heterogeneous distribution of calcium handling proteins within the t-tubule may be required for SCS, when the sarcoplasmic reticulum (SR) is inhibited. It also provides a foundation for further studies on the effects of three-dimensional t-tubule geometry and ion channel distribution on calcium dynamics with and without SR.

Bio: Kathy Lu is a research assistant professor in the Bioengineering department at the University of Illinois. She is interested in working on simulation of calcium dynamics in cardiac myocytes using distributed reaction-diffusion system solver.