doi: 10.1161/CIRCEP.107.748467
Original Articles |
Distinguishing Properties of Cells From the Myocardial Sleeves of the Pulmonary Veins
A Comparison of Normal and Abnormal Pacemakers
From the Faculty of Biological Sciences, University of Leeds, Leeds, UK (M.K.L.); Biomedical Sciences, University of Hull, Kingston-Upon-Hull, UK (S.A.J.); Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan (M.Y., H.H.); School of Medicine, University of Manchester, Manchester, UK (J.O.T., M.R.B.); and the School of Biomedical Sciences, University of Nottingham, Nottingham, UK (R.B.).
Correspondence: Correspondence to Dr Matthew K. Lancaster, Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom. E-mail m.k.lancaster{at}leeds.ac.uk
Received October 25, 2007; accepted February 5, 2008.
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 (PVm) 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 PVm, 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 PVm were smaller than atrial cells and showed large elevations in diastolic calcium during activation at physiological rates, a feature the PVm cells shared with cells from the sinoatrial node. Unstimulated spontaneous activity was observed in a minority of cells from the PVm, 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 PVm 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 PVm share some features with cells from the sinoatrial node but also have distinctly unique features that predispose them to the development of spontaneous activity.
Key Words: arrhythmia • pacemakers • pulmonary vein • sinoatrial node • intracellular calcium • atria