Integrative Structurally Detailed Model of Calcium Dynamics in the Cardiac Diad

In heart muscle, excitation‐contraction coupling translates electric signals into contraction of the heart. Excitation‐contraction coupling in cardiac myocytes (heart muscle cells) depends crucially on calcium‐induced calcium release (CICR) in a small microdomain known as the diad. In this study we develop methods for describing CICR at the structurally detailed level of the diad as well as develop methods by which these models may be simplified for use at the level of cell and tissue. In particular, the method enables description of diad geometry, spatial configuration of proteins within the diad, the motion and distribution of Ca²⁺ ions within the diad, and Ca²⁺ ion binding to receptor sites on L‐type Ca²⁺ channels and sarcoplasmic Ca²⁺ release channels. The end result of modeling is a biophysically detailed, computationally efficient model of CICR. Such a model enables investigation of a wide variety of biologically interesting issues in cardiac electrophysiology involving detailed descriptions of excitation‐contraction coupling using multiscale models of heart muscle.