Transcriptomic Approaches to Modelling Long Term Changes in Human Cardiac Electrophysiology

Slow changes in the activity of the heart occur with time scales from days through to decades, and may in part result from changes in cardiomyocyte properties. The cellular mechanisms of the cardiomyocyte action potential have time scales from < ms to hundreds of ms. Although the quantitative dynamic relations between mRNA transcription, protein synthesis, trafficking, recycling, and membrane protein activity are unclear, mRNA-Seq can be used to inform parameters in cell excitation equations. We use such transcriptomic data from a non-human primate to scale maximal conductances in the O’Hara-Rudy (2011) family of human ventricular cell models, and to predict diurnal changes in human ventricular action potential durations. These are related to circadian changes in the incidence of sudden cardiac deaths. Transcriptomic analysis of human fetal hearts between 9 and 16 weeks gestational age is beginning to be used to inform ventricular cell and tissue models of the electrophysiology of the developing fetal heart.