The Characteristics of Spontaneous Action Potential of Cardiac Myocytes in Rabbit Pulmonary Veins

ABSTRACT

BACKGROUND AND OBJECTIVES: Atrial fibrillation is one of the most prevalent arrhythmia with clinical significance. Recently, some subset of paroxysmal atrial fibrillation was reported to be originated from a focal, rapidly firing source inside the large thoracic veins, such as pulmonary veins, superior vena cava and coronary sinus. The pulmonary veins are known to be the most frequent source of this type of atrial fibrillation. The proximal segment of pulmonary vein was reported to be made up with cardiac muscle cells. This study was performed 1)to define the characteristics of action potential of cardiac myocytes inside the rabbit pulmonary vein in single cell preparation, 2)to observe the changes in action potential and current activation to acetylcholine and isoproterenol, and 3)to compare these changes with those in atrial myocytes. METHOD AND RESULTS: In most of rabbit specimens, myocardial tissue extended over the pulmonary vein for a few millimeters(1-2.5mm). Single atrial myocyte and myocyte in pulmonary vein were successfully isolated. With using whole cell patch clamp technique, spontaneous activities of action potentials(APs) with diastolic depolarization were observed in 75% of pulmonary vein myocytes, in contrast to the absence of spontaneous activity in atrial myocytes. During spontaneous APs of pulmonary vein myocytes, the maximal diastolic potential was -50.5+/-6.5 mV and peak potential was 32.5+/-9.5 mV, and the frequency of APs was 1-2.5 Hz. During perfusion of isolated pulmonary vein myocytes with acetylcholine, resting membrane potential was hyperpolarized and spontaneous APs activity was markedly reduced or completely disappeared. These effects were observed in very low concentration of acetylcholine, even with 1-2 nM. The analysis of change of currents by applying step pulse revealed this response was mediated by activation of IK(ACh) and the current change was more prominent in pulmonary vein myocytes than atrial myocytes. The responses of these cells to isoproterenol were variable from increased spontaneous APs to inhibition of APs. CONCLUSION: This study revealed that pulmonary vein myocytes was another automatic pacemaking focus, same as sinoatrial nodal and Purkinje cells. These characteristics explain why focal atrial fibrillation was frequently initiated inside pulmonary veins.