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The Carmeliet-Coraboeuf-Weidmann Lecture 2012

“The cardiac action potential - a never ending story of ions, channels, drugs and disease”

Ursula RavensUrsula Ravens obtained her medical degree from Albert-Ludwigs-University of Freiburg in 1969. While still in medical school she started experimental work in the electrophysiology lab at the Department of Physiology. After a short interim in clinical medicine for her internship she joined Heinz Lüllmann, head of the Department of Pharmacology at the University of Kiel, as a research fellow in 1970. After doing her “Habilitation” in 1979, she spent some time as a guest scientist with Gerrit Isenberg at the University of Homburg. In 1985 she obtained her first permanent position as a Professor of Cardiovascular Pharmacology at Essen University. After a sabbatical at Imperial College London in 1995 with Sian Harding she was appointed full Professor of Pharmacology and Toxicology at the Medical Faculty of Dresden University of Technology, where she moved to in 1997.

Dr. Ravens has participated in the “working group” meetings from the very start and served as chairperson of EWGCCE 1996-1998. Together with her long-time collaborator Erich Wettwer, she organised the 1996 meeting in Essen and the 2001 meeting in Dresden. In 2004, she also organised the European Section meeting of the International Society for Heart Research in Dresden and was President of the 2004 Annual Meeting of the German Cardiological Society in Mannheim. She has served as a member of the Editorial Board of Cardiovascular Research, Journal of Molecular and Cellular Cardiology, European Journal of Pharmacology, Europace, Naunyn-Schmiedeberg’s Archives of Pharmacology. She is a Fellow of the European Society of Cardiology and of the American Heart Association, and is an elected member of the German National Academy of Medicine and Sciences “Leopoldina”. She holds a doctor-honoris-causa title of the University of Szeged, and a honorary professorship in cardiology from the Military Postgraduate Medical School Beijing.

Dr. Ravens’ research interests have been in cardiovascular pharmacology in health and disease. Combining action potential and force of contraction measurements, she studied many of the then fashionable drugs like digitalis glycosides, phosphodiesterase 3 inhibitors, sodium channel modulating toxins on cardiac excitation-contraction coupling and came to the conclusion that membrane potential does not control contraction, but only modulates force development depending on the underlying ion mechanism of change in action potential morphology. The then novel single-electrode voltage clamp technique, learnt in Homburg, Saar, provided a useful tool for dissecting drug effects on ion channels.

In Dresden, she has focused on electrical remodeling in cardiac disease, with particular  emphasis on atrial fibrillation, trying to understand the impact of disease-related functional alterations on responses to drug. For instance, selective ion channel blockers which are precisely analysed in expression systems may not exert their anticipated effects in native myocardium because of disease-induced remodeling. During the past decade she has also devoted part of her time to the regenerative potential of stem cells and progenitor cells as possible sources for tissue engineering. 

Her life is not all work.  She is married to Gunther (a Professor of Medicine and veteran of many Working Group meetings) and they have one daughter.

Edward CarmelietEdward Carmeliet
Silvio Weidmann Silvio Weidmann
Edouard Coraboeuf Edouard Coraboeuf
This lecture has been established to celebrate the contributions that Edward Carmeliet, Edouard Coraboeuf and Silvio Weidmann have made to cardiac cellular electrophysiology. It also recognizes their roles in establishing the Working Group in Cardiac Cellular Electrophysiology, which later became part of the European Society of Cardiology.  With the kind permission of Edward Carmeliet and the families of Edouard Coraboeuf and Silvio Weidmann, the lectureship  is awarded annually to an outstanding European Cardiac Cellular Electrophysiologist.

The story begins with Silvio Weidmann (1921-2005).  After  studying medicine at the University of Bern, in 1948 he went to the University of Cambridge to work with Alan Hodgkin and Andrew Huxley who were at that time well on their way to elucidating the properties of the nerve action potential. In Cambridge, Silvio was joined by Edouard Coraboeuf (1926- 1998).  Together, in 1949, they published the first intracellular recording of a cardiac action potential. Edward Carmeliet also worked with Silvio Weidmann, in his case in Bern where he carried out his PhD with pioneering studies on the potassium and chloride permeability of the heart.

All three continued to make outstanding contributions to cardiac electrophysiology. Silvio Weidmann demonstrated the low conductance of the plateau of the action potential and the voltage dependence of the sodium channel as well as its sensitivity to local anaesthetics.  He also demonstrated the diffusion of potassium between cells. Edouard Coraboeuf went on to identify early afterdepolarizations which lead to torsades-de-pointes arrhythmias. He subsequently pioneered cellular studies on the human heart as well as characterizing the maintained component of the sodium current and its contribution to the plateau of the action potential. As mentioned above, Edouard and Edward had both worked with Silvio.  Subsequently the two collaborated on work characterizing the chloride current. Edward Carmeliet  (1930-) also pioneered studies of the control of the action potential duration; in particular the effects of heart rate and metabolism. He published seminal papers on virtually every cardiac potassium channel and on the mechanisms of action of antiarrhythmic agents. He also demonstrated the interaction of ionic gradients with channels and transporters.

As well as their own scientific contributions, all three have established their own schools of research as represented by countless successful careers of younger scientists worldwide.
Our Working Group owes much to this trio. Edward Carmeliet organized the first meeting in Leuven in 1977. The next year Edouard Coraboeuf organized a meeting in Orsay and, in 1980, the Working Group met in Bern at the invitation of Silvio Weidmann.

The Working Group of Cardiac Cellular Electrophysiology provides an informal environment to discuss ion channels, cell-signaling, excitation-contraction coupling and other topics related to myocardial function.

 This lecture has been generously sponsored by Cairn Research