Project
The involvement of the pulmonary vein in atrial fibrillation and how it is affected by co-morbidities
Supervisor(s)
Dr Robert Drummond, Dr Edward Rowan
Area
Cardiovascular pharmacology
Description
Atrial fibrillation is the most common cardiac arrhythmia that is encountered clinically and it is associated with significant morbidity and mortality. One of the most significant triggers for this type of arrhythmia is ectopic electrical activity originating within the pulmonary veins. The pulmonary veins are somewhat unusual in that they are surrounded by an external sleeve of cardiomyocytes and it is this sleeve which is believed to be responsible for generating the ectopic electrical activity. However, the cellular mechanisms that underlie the ectopic activity in the pulmonary vein are unknown. Our hypothesis is that intracellular Ca2+ plays a key role in regulating the electrical properties of the cardiomyocytes and factors that alter Ca2+ signalling will contribute to their arrhythmogenic tendency. This project will examine the relationship between Ca2+ and electrical activity in cardiomyocytes of intact sections of the pulmonary veins as well as in single cells, obtained from healthy animals as well as disease models for pulmonary hypertension. Through a greater understanding of the cellular mechanisms underlying the electrical activity within the pulmonary vein, potential novel therapeutic targets to treat atrial fibrillation will be identified.
Techniques
Fluorescence microscopy, Measurement of intracellular Ca2+ concentration, Electrophysiology
References
Lip GY, Fauchier L, Freedman SB, Van Gelder I, Natale A, Gianni C, Nattel S, Potpara T, Rienstra M, Tse HF, Lane DA. Atrial fibrillation. Nat Rev Dis Primers. 2016 Mar 31;2:16016. doi: 10.1038/nrdp.2016.16.
Rietdorf K, Masoud S, McDonald F, Sanderson MJ, Bootman MD. Pulmonary vein sleeve cell excitation-contraction-coupling becomes dysynchronized by spontaneous calcium transients. Biochem Soc Trans. 2015 Jun;43(3):410-6. doi: 10.1042/BST20140299.
Logantha SJ, Cruickshank SF, Rowan EG, Drummond RM. Spontaneous and electrically evoked Ca2+ transients in cardiomyocytes of the rat pulmonary vein. Cell Calcium. 2010 48 (2-3): 150-60. doi: 10.1016/j.ceca.2010.08.002.