Simulation of spontaneous action potentials of cardiomyocytes in pulmonary veins of rabbits

Abstract

Atrial fibrillation is the most prevalent arrhythmia, but the mechanisms by which it develops are not clear. Recently, over 90% of paroxysmal atrial fibrillation was found to be located inside the main pulmonary veins (PVs). We found that single cardiac myocytes isolated from the main PVs of rabbits generate spontaneous action potentials (SAP). We therefore assayed the electrical characteristics of these cardiomyocytes. Among the diverse ionic currents identified were INa, ICa,L, IK1, IKr, IKs, Ito, IKsus, Incx, Ipump, IKH and ICl,Ca. In contrast, IK1 was minimal, IKs could be detected only in the presence of 10 microM forskolin, and we were unable to detect If and ICa,T, the most important currents for pacemaking activity in sinoatrial node cells. To identify the main cause of SAP, we developed a model that can explain the electrical properties of these cardiomyocytes. After reconstructing the ionic currents based on experimental observations, we were able to use our model to successfully reconstruct the characteristics of the SAP of PV cardiomyocytes. The simulation showed that the major currents contributing to pacemaking depolarization were ICaL, IKr, a background current and Na+-K+ pump current. Deactivation kinetics of IKr was one of the major determinants of the rate of pacemaking depolarization. The steady state inactivation of Ito was shifted to the negative voltage and the activity of Ito was minimal in the range of the SAP. The major currents for the repolarization were IKr and Ipump. The amplitude of most currents in these cardiac myocytes was small and no currents did not exceed 30 pA during the SAP, indicating that slight activation of other inward or outward currents will have profound effects on the SAP. To our knowledge, this report is the first to show the simulation of SAP of PV cardiomyocytes. This model may help to study on the electrophysiological basis of paroxysmal atrial fibrillation originating from PVs.