Spontaneous Ca2+ signalling and ultrastructural changes in pulmonary vein sleeve cells during ageing – risk factors for atrial fibrillation?

Rietdorf, Katja; Masoud, Said; McDonald, Fraser and Bootman, Martin (2014). Spontaneous Ca2+ signalling and ultrastructural changes in pulmonary vein sleeve cells during ageing – risk factors for atrial fibrillation? In: 13th International Meeting of the European Calcium Society, 13-17 Sep 2014, Aixe-en-Provence, France.

Abstract

Atrial fibrillation (AF) is the most common form of a sustained cardiac arrhythmia, with age and obesity being the most significant risk factors for developing atrial fibrillation. 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. Since ageing is a major risk factor for AF development, we investigated differences in the ultrastructure of PVCs, and we used Ca2+ imaging to measure spontaneous and electrically-paced Ca2+ signals in mice of 3 and 24 month of age. In slices from 24 month-old mice we found a higher incidence of spontaneous Ca2+ signals, and an increased resistance to electrical pacing, both of which are known triggers of arrhythmic events in the heart. Using scanning electron microscopy, we found a striking difference in the density of mitochndria in PVCs from young and old mice. PVCs from 24 month-old mice contained a greater density of mitochondria of heterogeneous shapes. Sionce mitochondria are the most significant buffers of cytosolic Ca2+ changes in cardiomyoctes, it is plausible that an increased mitochondrial density will significantly alter the spatial and temporal properties of PVC Ca2+ signalling, and they could potentially act as an additional Ca2+ source in the cells, thereby contributing to the pro-arrhythmic activity found in PVCs from older mice.

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