title: Pulmonary vein sleeve cell excitation-contraction-coupling becomes dysynchronized by spontaneous calcium transients.
abstract: Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. Substantial evidence indicates that cardiomyocytes located in the pulmonary veins [pulmonary vein sleeve cells (PVCs)] cause AF by generating ectopic electrical activity. Electrical ablation, isolating PVCs from their left atrial junctions, is a major treatment for AF. In small rodents, the sleeve of PVCs extends deep inside the lungs and is present in lung slices. Here we present data, using the lung slice preparation, characterizing how spontaneous Ca2+ transients in PVCs affect their capability to respond to electrical pacing. Immediately after a spontaneous Ca2+ transient the cell is in a refractory period and it cannot respond to electrical stimulation. Consequently, we observe that the higher the level of spontaneous activity in an individual PVC, the less likely it is that this PVC responds to electrical field stimulation. The spontaneous activity of neighbouring PVCs can be different from each other. Heterogeneity in the Ca2+ signalling of cells and in their responsiveness to electrical stimuli are known pro-arrhythmic events. The tendency of PVCs to show spontaneous Ca2+ transients and spontaneous action potentials (APs) underlies their potential to cause AF.
authors.affiliation: *Department of Life, Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes, MK7 6AA, U.K.
authors.forename: Katja
authors.initials: K
authors.lastname: Rietdorf
authors.affiliation: *Department of Life, Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes, MK7 6AA, U.K.
authors.forename: Said
authors.initials: S
authors.lastname: Masoud
authors.affiliation: †Department of Orthodontics, Floor 22, Tower Wing, St. Thomas St, King's College London Dental Institute, London, SE1 9RT, U.K.
authors.forename: Fraser
authors.initials: F
authors.lastname: McDonald
authors.affiliation: ‡Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655, U.S.A.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sanderson
authors.affiliation: *Department of Life, Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes, MK7 6AA, U.K.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Bootman
mesh_terms: D000200:Action Potentials / Q000502:physiology; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics*; D006325:Heart Atria / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D011667:Pulmonary Veins / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002118:Calcium