Population-Level Modeling of Cardiac Nonlinear Dynamics

Abstract

The nonlinear dynamics of cardiac excitable waves is controlled by ion channels that are the basic molecular building blocks of the heart's electrical circuitry. Variations in gene expression and protein levels can cause the conductance of those channels to vary both between cells of the same heart and between hearts of different individuals in a genetically diverse population.

This talk will discuss the results of recent computational modeling and experimental studies aimed at identifying electrophysiological parameter sets that represent different individuals in a genetically diverse population and at distinguishing intra-heart cell-to-cell from inter-individual variability.

Our main finding is that feedback sensing of the intracellular calcium concentration suffices, remarkably, to constrain parameter sets so as to produce a normal electrophysiological phenotype without any constraint on the electrical signal due to compensation between different ionic currents. Furthermore, parameter sets can differ greatly such that different individuals may respond very differently to environmental stresses and drug therapies. The results have important implications for understanding cardiac homeostasis and developing personalized therapies.