Nanodomain-delimited remodelling in atrial fibrillation
Atrial fibrillation (AF), the most common cardiac arrhythmia and the leading cause of cardioembolic stroke, is associated with remodelling of membrane receptors and alterations in the cAMP-dependent regulation of Ca2+-handling mechanisms. For instance, decreased L-type Ca2+ current (ICa,L) density but upregulated ryanodine receptors (RyR2), are major hallmarks of AF. These inhomogeneous AF-associated changes in protein phosphorylation point to a local regulation of cAMP within these intracellular compartments.
Although compartmentalised cAMP/cGMP signalling is now recognised to be crucial for cardiac excitation-contraction coupling and it is known to regulate a plethora of pathophysiological processes in the ventricle, the regulation and function of local cyclic nucleotide signalling in the atria remains unexplored. It is also unclear whether the same processes apply in humans.
By combining classical electrophysiological and molecular techniques with state-of-the-art imaging methods for real-time measurement of cAMP/cGMP, we aim to define cyclic nucleotide nanodomains and how their compartmentalised signalling regulates Ca2+-handling function and dysfunction in the human atria. Our work provides a molecular basis for new atrial-specific therapeutic targets for the treatment of AF.
Date:
16 May 2023, 14:30 (Tuesday, 4th week, Trinity 2023)
Venue:
Sherrington Library, off Parks Road OX1 3PT
Speaker:
Cristina E. Molina, PhD (Institute of Experimental Cardiovascular Research, University Centre of Cardiovascular Science (UCCS), University Medical Centre Hamburg)
Organising department:
Department of Physiology, Anatomy and Genetics (DPAG)
Organiser:
Professor Manuela Zaccolo MD (DPAG, University of Oxford)
Organiser contact email address:
manuela.zaccolo@balliol.ox.ac.uk
Host:
Professor Manuela Zaccolo MD (DPAG, University of Oxford)
Part of:
Cardiac Sciences Theme Guest Speakers
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Talitha Smith
