DC4
Modelling the effects of CoA metabolism on the electrical activity of the heart
Background: Recent work has shown a link between deficiency in CoA biosynthesis and increased propensity to arrhythmia. In particular, patients with mutation in PPCS have been shown to be at increased risk to develop dilated cardiomyopathy. How CoA biosynthesis deficiencies lead to arrhythmogenicity is currently unknown.
Objectives: (1) Develop a highly detailed model of cardiomyocyte electrophysiology that includes a detailed representation of energetics and CoA synthesis. (2) Elucidate the link between CoA biosynthesis and its role in modifying the cardiac action potential. (3) Perform 3D simulations in patient-specific geometries of both healthy and cardiomyopathic hearts to investigate how subcellular changes and geometric abnormalities contribute towards increased propensity towards arrhythmia generation.