https://doi.org/10.36866/pn.131.46

Professor Richard W. Tsien
Druckenmiller Professor of Neuroscience, Department of Neuroscience and Physiology, New York University.

Professor Emeritus Hartmut Porzig Department of Pharmacology, University of Bern, Switzerland
Richard W. Tsien was a close scientific colleague and friend of Harald Reuter. Hartmut Porzig was a senior research fellow and long-time co-worker of Harald Reuter at the Department of Pharmacology, University of Bern, Switzerland.

On 22 February 2022, the eminent physiologist and pharmacologist Professor Harald Reuter died in Bern, Switzerland at 87 years of age. Through his pioneering investigations on voltage-gated cardiac calcium (Ca2+) channels and on regulation of intracellular Ca2+ concentrations, Reuter became one of the founding fathers of research on Ca2+-mediated signal transduction. His work also provided the basis for understanding the cardiac actions of the autonomic nervous system and sympathetic neurotransmitters, and it helped explain the mechanisms of action of cardiac glycosides and Ca2+-antagonist drugs.

Reuter was born in Düsseldorf, Germany in 1934 as the son of an attorney. After earning a medical degree, he joined the Pharmacological Institute at the University of Mainz where he completed his doctoral thesis in 1960 and obtained his habilitation in 1965.

During a research stay in 1966 at the Institute of Physiology at the University of Bern, Switzerland, he collaborated with Silvio Weidmann, a pioneer of electrophysiological investigations in mammalian Purkinje cells. They were the first to demonstrate the presence of a voltage-gated Ca2+ inward current that supported the plateau phase of the cardiac action potential (Reuter, 1967). Following this, Reuter then worked with GW Beeler as an assistant professor at the Mayo Clinic in Rochester, Minnesota, to achieve a quantitative analysis of these Ca2+ currents and their role in activating myocardial muscle contraction.

In parallel with his work on voltage-gated Ca2+ movements into myocardial cells, Reuter began working with Norbert Seitz to study Ca2+ outward movements in an uphill flux against the ion’s electrochemical gradient. They discovered that this transport was mainly achieved via a Na+/Ca2+ exchange, using the inwardly directed electrochemical gradient for Na+ to expel Ca2+ in the opposite direction and thus maintain a low intracellular Ca2+ concentration. After finishing a manuscript describing this work (Reuter and Seitz, 1968), Reuter learned that Blaustein and Baker in the group of Allan Hodgkin at the University of Cambridge had simultaneously studied a similar exchange system in squid axons. When Reuter and Blaustein met at an international Congress in 1968 they started a long-lasting friendship that subsequently led to a successful collaboration.

In 1969 Reuter accepted the offer for a tenured position as Professor of Pharmacology at the University of Bern, Switzerland. At the time, the Pharmacological Institute was headed by Walter Wilbrandt, a pioneer in the quantitative analysis of membrane transport processes, whose work and thinking impressed Reuter deeply. In 1972, Reuter succeeded Wilbrandt as head of the institute. During his entire academic career until his retirement in 1999, Reuter remained loyal to the University of Bern even though he received several offers for attractive positions at universities in Germany and the United States.

Originally a German citizen, Reuter took up Swiss citizenship in 1987. He maintained an extended network and continuous scientific exchange with leading research groups in England and the US. For example, he enjoyed several sabbatical visits to Yale and Stanford. At the same time, his own laboratory in Bern attracted both young and established researchers from Switzerland and abroad.

In 1977, Reuter and Beeler used their earlier investigations and developed them with other evidence to formulate a broadly accepted mathematical model integrating all known ion currents that contribute to the myocardial action potential. The experimental basis of this project required tissue samples from calf and sheep hearts freshly obtained from the local slaughterhouse. This was quite popular with other members of his group, not only for the fascinating science but also for the delicious ragout prepared from calf hearts by Reuter’s wife Liselotte.

The complex structure of the multicellular preparations used in these electrophysiological experiments made it very difficult to separate unequivocally membrane Ca2+currents from other overlapping membrane currents. To circumvent these difficulties, the novel patch clamp technique developed by Erwin Neher and Bert Sakman offered an elegant way to allow a detailed kinetic analysis of single myocardial ion channels. To adapt this method to cultured cardiac muscle cells, Reuter convinced Neher to join him, along with two other eminent colleagues with strong biophysical interests, David Colquhoun (London) and Chuck Stevens (Yale), for an intensive “Summer Camp” in Bern.

As a byproduct of the exchange of experimental know-how, the group discovered that intracellular Ca2+ activated a previously unknown membrane channel mediating a voltage-independent inward movement of cations. Reuter dubbed it the CNRS channel, an acronym derived from authors’ last names, thus rivalling the famous French research organisation with the same four-letter acronym. A few months later, Reuter, Stevens, Richard Tsien and Gary Yellen published a detailed kinetic analysis of single cardiac Ca2+ channels (Reuter et al., 1982). Soon thereafter, Reuter leveraged patch clamp methods to study effects of adrenaline on single Ca2+ channels.

Later, other research groups showed that in addition to the L-type Ca2+ channels dominating in myocardial cells, various excitable tissues contained other types of voltage-gated Ca2+ channels with different kinetic, pharmacological, and molecular properties. Beyond electrophysiology, Reuter never hesitated to adopt novel methodological approaches, like confocal or fluorescence microscopy or molecular biology, in order to gain deeper insights into the effects of drugs or neurotransmitters on cellular Ca2+ handling in excitable tissues.

Reuter was a passionate and exceptionally skilled experimenter with a strong commitment to hands-on experimental work. Consequently, for most of the original papers he published during his scientific career, he himself contributed an important part of the experimental results.

Reuter gained many awards and honours for his scientific achievements. These included the Marcel-Benoist Prize, Switzerland’s most prestigious Science Award, the Schmiedeberg award of the German Pharmacological Society, the K.S. Cole award of the US Biophysical Society, honorary memberships of the Belgian Royal Academy of Medicine and of The Physiological Society, London. He was a chosen member of several scientific academies, among them the German National Academy Leopoldina and the National Academy of Sciences USA. As chair of the Committee for Human Rights of the Swiss Academies and of the International Network of Academies and Scholarly Societies he was a committed advocate of scientists in precarious working and living conditions.

Reuter was a very good and mindful teacher and mentor. He supported his co-workers generously while leaving them much freedom to pursue their own projects. He almost never lost his temper, but would feel physically ill if someone cast doubt on his careful experimental work or his scientific integrity.

Privately, he was an impressive personality, inquisitive and multi-talented, blessed with a dry yet warm sense of humour. For many years he played the violin and enjoyed skiing in the Swiss mountains. He collected works of fine art, cultivated acquaintances with contemporary painters and enjoyed a long-standing friendship with an eminent Swiss gallerist. During trips to Japan, Reuter and his wife Liselotte met several well-known ceramicists and brought back a small but beautiful collection of Japanese ceramics.

He was happily married to Liselotte, a doctor and fellow student, for more than 50 years. The pair complemented each other perfectly. They were proud of their three children and eight grandchildren. They enjoyed a large circle of friends and generously shared their lovely home and hospitality. Each year all members of the institute were invited to a festive summer party in their house and garden overlooking a lake close to the city of Bern.

The death of Liselotte from cancer in 2015 affected him deeply and cast a shadow over his last years. Reuter’s passing marks the loss of an unforgettable personality, a dear friend, great scientist and teacher.

References

Reuter H (1967). The dependence of slow inward current in Purkinje fibres on the extracellular calcium concentration. Journal of Physiology 192, 479-492. https://doi.org/10.1113/jphysiol.1967.sp008310

Reuter H, Seitz N (1968). The dependence of calcium efflux from cardiac muscle on the temperature and external ion composition. Journal of Physiology 195, 451-470. https://doi.org/10.1113/jphysiol.1968.sp008467

Reuter H et al. (1982). Properties of single calcium channels in cardiac cell culture. Nature 297, 501-504. https://doi.org/10.1038/297501a0