MATHEMATICAL-MODEL OF AN ADULT HUMAN ATRIAL CELL - THE ROLE OF K+ CURRENTS IN REPOLARIZATION

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