The 2025 Summer Term Cardiac Function Seminar series talks will be back Thursday 1st May 2025 when we will be welcoming Professor Cristina E. Molina, University Medical Center Hamburg-Eppendorf, Germany.
Talk Title: Decoding heart beat dance: Role of PDEs in controlling Ca2+ dynamics and arrhythmias in the human heart
Talk Time: 12:30 – 13:30 UK time
Location: Hybrid Meeting (Hybrid – online Via Teams and Meeting room 427/428 4th Floor ICTEM, Hammersmith Campus, Du Cane Road W12 0NN
Please note the seminar organizers and the Head of Section would like to request that attendees will in the majority of cases be physically present in the seminar room and a participation via Teams shall be the exception.
Short Bio:
Cristina E. Molina is a professor at the University Medical Center Hamburg-Eppendorf in Germany and a visiting professor at the University of Oxford in the UK. She has 20 years of experience as a cardiac cellular electrophysiologist. She obtained her PhD from the Universitat Autonoma de Barcelona in 2009 and did her first post-doctoral work at the University of Paris 11. After her IEF Marie Curie fellowship at the Cardiovascular Research Centre in Barcelona, she moved to Germany in 2015. She obtained a full professor Heisenberg position in 2024, together with her visiting professor status at the DPAG in Oxford. She studies pathophysiological aspects of cardiac EC coupling and arrhythmogenesis in human cardiac cells. She is best known for her work on the role of receptor-mediated modulation of ionic currents, intracellular Ca2+-handling and second messengers in atrial fibrillation, including the contribution of different phosphodiesterases to the pathophysiological mechanisms underlying this arrhythmia. She has developed an isolation method that allows her to transduce and culture undifferentiated human primary cardiac myocytes and neurons from any type of human cardiac tissue, from centimetre to millimetre sized tissue, atrial or ventricular, from healthy or diseased patients.
Talk Description:
Atrial fibrillation (AF) is the most common sustained arrhythmia in the clinical setting and is associated with significant morbidity and mortality. AF is also associated with severe cellular calcium (Ca2+)-handling abnormalities in atrial myocytes, which may contribute to the initiation and maintenance of the arrhythmia. This so-called “remodeling” is supposed to involve abnormal phosphorylation of key proteins of cellular Ca2+ handling. In addition, previous studies suggest that impaired phosphodiesterases (PDEs)-dependent regulation of the spatiotemporal distribution of cAMP may contribute to Ca2+-handling abnormalities associated with AF.
The cAMP signaling pathway plays a key role in the regulation of cardiac contractility, relaxation, automaticity, metabolism and gene expression. A few years ago it was shown that there is a specificity in the cAMP signals generated upon activation of different Gs protein-coupled receptors (GsPCR). A characteristic feature of each GsPCR to induce a specific functional response is a tight control of the cAMP signal by specific PDEs. Several groups have been characterizing the role of PDEs in ventricular myocytes from animal models, but only few studies have evaluated the importance of PDEs in human heart and almost none of them are related to the atria. Our recent studies have demonstrated the expression and functional role of different PDE1, PDE2, PDE3, PDE4 and PDE8 isoforms in the human atria. We have shown the role of PDE4 in Ca2+-handling in human atrial myocytes from healthy patients. Furthermore, we recently showed that PDE8B co-localize with the L-type Ca2+-channel in human atrium and it accumulates in this channel in samples from patients with AF contributing to the reduction of ICa,L and the shortening of the action potential duration.
We investigate the role of PDEs and GsPCR in the AF-associated remodelling of cellular Ca2+-handling and atrial arrhythmogenesis by measuring the real-time cyclic nucleotides levels, L-type Ca2+ current, spontaneous Ca2+ releases from the sarcoplasmic reticulum, sarcoplasmic reticulum Ca2+ content, protein expression and localization, using highly sensitive and specifically targeted FRET biosensors, patch-clamp, confocal Ca2+ imaging, sharp electrode, contractility measurements and biochemical experiments in living human cardiac myocytes, neurons and tissues.
If you are joining online and you have not yet signed up to join the Cardiac Function Seminar Team group in order to participate in the seminar online please register via the linked tab or here which will provide access to the Team.
Please do this ahead of time of the talk.
The Cardiac Function Seminar Team
(Prof. Thomas Brand, Natasha Richmond)
