Development of biophysically detailed electrophysiological models for pacemaking and non-pacemaking human pulmonary vein cardiomyocytes

Ectopic foci originating from the pulmonary veins (PVs) have been suggested as the underlying cause for generating atrial arrhythmias that include atrial fibrillation (AF). Recent experimental findings indicate two types of PV cells: pacemaking and non-pacemaking. In this study, we have developed two mathematical models for human PV cardiomyocytes with and without pacemaking activities. The models were reconstructed by modifying an existing model of the human right atrium to incorporate extant experimental data on the electrical differences between the two cell types. Differences in their action potential (AP) profiles and automaticity were reproduced by the models, which can be attributed to the observed differences in the current densities of I_NCX, I_to, I_Na and I_Ca-L, as well as the difference in the channel kinetics of I_Ca-L and inclusion of the I_f and I_Ca-T currents in the pacemaking cells. The developed models provide a useful tool suitable for studying the substrates for generating AF.