Background— A common source of arrhythmogenic spontaneous activity instigating atrial fibrillation is the myocardial tissue, or sleeves, at the base of the pulmonary veins. This study compared the properties of cells from the myocardial sleeves of the pulmonary veins (PV_m) with cells from the normal cardiac pacemaker (the sinoatrial node) and regions of the atria. Our objective was to identify key features of these cells that predispose them to becoming the focus of cardiac arrhythmias.

Methods and Results— Single cells were isolated from samples of rabbit PV_m, central and peripheral sinoatrial node, crista terminalis, and left and right atria. Detailed morphology of cells was assessed and intracellular calcium concentrations measured with the use of Fluo-3. Cells from the PV_m were smaller than atrial cells and showed large elevations in diastolic calcium during activation at physiological rates, a feature the PV_m cells shared with cells from the sinoatrial node. Unstimulated spontaneous activity was observed in a minority of cells from the PV_m, but numerous cells from this region showed spontaneous activity for a brief period immediately subsequent to stimulation at physiological rates. This was not observed in atrial cells. Assessment of calcium removal pathways showed sarcolemmal calcium extrusion in cells from the PV_m to have a high reliance on “slow” extrusion pathways to maintain intracellular calcium homeostasis because of a low expression of sodium–calcium exchanger.

Conclusions— We conclude that cells from the PV_m share some features with cells from the sinoatrial node but also have distinctly unique features that predispose them to the development of spontaneous activity.