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

Masoud, Said; Bootman, Martin D.; McDonald, Fraser and Rietdorf, Katja (2014). Spontaneous Ca2+ signalling and ultrastructural changes in pulmonary vein sleeve cells during ageing – risk factors for atrial fibrillation? In: Calcium Signalling: The Next Generation, 9-10 Oct 2014, London, UK.

URL: http://www.biochemistry.org/

Abstract

Atrial fibrillation (AF) is the most common form of a 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. 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 mitochondria in PVCs from young and old mice: PVCs from 24 month-old mice contained a greater density of mitochondria of heterogeneous shapes. Since mitochondria are the most significant buffers of cytosolic Ca2+ changes in cardiomyocytes, 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.

Viewing alternatives

Item Actions

Export

About

Recommendations