Multiscale Modeling of Dyadic Structure-Function Relation in Ventricular Cardiac Myocytes

Cardiovascular disease is often related to defects of subcellular components in cardiac myocytes, specifically the dyadic cleft, which include changes cleft geometry and channel placement. Modeling these pathological requires both spatially resolved as well whole cell level descriptions. We use a multiscale model create structure-function relationships explore impact molecular on electrophysiology calcium cycling. This incorporates stochastic simulation individual L-type channels ryanodine receptor channels, detailed concentration dynamics clefts, rabbit membrane potential dynamics, system partial differential equations for myoplasmic lumenal free Ca2+ Ca2+-binding molecules bulk cell. found action duration, systolic, diastolic [Ca2+] respond most sensitively current. The cluster structure inside clefts was affect all biomarkers investigated. shape clusters observed experiments by Jayasinghe et al. density within (characterized mean occupancy) showed strongest correlation effects biomarkers.