Mathematical model of an adult human atrial cell: the role of K+ currents in repolarization

Abstract

We have developed a mathematical model of the human atria myocyte based on averaged voltage-clamp data recorded from isolated single myocytes. Our model consists of a Hodgkin-Huxley-type equivalent circuit for the sarcolemma, coupled with a fluid compartment model, which accounts for changes in ionic concentrations in the cytoplasm as well as in the sarcoplasmic reticulum. This formulation can reconstruct action potential data that are representative of recordings from a majority of human atrial cells in our laboratory and therefore provides a biophysically based account of the underlying ionic currents. This work is based in part on a previous model of the rabbit atrial myocyte published by our group and was motivated by differences in some of the repolarizing currents between human and rabbit atrium. We have therefore given particular attention to the sustained outward K+ current (I[sus]), which putatively has a prominent role in determining the duration of the human atrial action potential. Our results demonstrate that the action potential shape during the peak and plateau phases is determined primarily by transient outward K+ current, I(sus) and L-type Ca2+ current (I[Ca,L]) and that the role of I(sus) in the human atrial action potential can be modulated by the baseline sizes of I(Ca,L), I(sus) and the rapid delayed rectifier K+ current. As a result, our simulations suggest that the functional role of I(sus) can depend on the physiological/disease state of the cell.