Michel Lazdunski, Specialist of Ion Channels,
Receives CNRS Gold Medal for the Year 2000

Paris, September 28, 2000

The CNRS Directorate General has awarded the CNRS Gold Medal for the year 2000 to Michel Lazdunski, professor at the Medical School of the University of Nice – Sophia Antipolis, and director of the CNRS Institute of Molecular and Cell Pharmacology. A world-renowned specialist of ion channels, Michel Lazdunski and his team have made internationally recognized contributions to basic research and to applied research in pharmacology and pathology. These range from understanding the mechanisms underlying antihypertensives, antidiabetics, and inhalational anesthetics, to the mechanisms of pain perception, cardiac arrhythmia, convulsions, and cerebral ischemia.

Michel Lazdunski was born on April 11, 1938 in Marseilles. He earned a degree in chemical engineering in 1959, followed by a Ph. D. in physical chemistry in 1962, and a doctorate in biochemistry (doctorat ès sciences) in 1964. He joined the CNRS in 1962 as an attaché de recherche with the CNRS Institute of Biochemistry in Marseilles. In 1964, he led a small group at this institute studying the physical chemistry of proteins. When the CNRS Center for Biochemistry and Molecular Biology opened in 1967 in Marseilles, he took charge of the research group studying the physical chemistry of proteins and enzymology, which he oversaw until 1973. He then created the CNRS Center for Biochemistry in Nice and directed it until 1989, when he founded the CNRS Institute of Molecular and Cell Pharmacology (Institut de pharmacologie moléculaire et cellulaire, IPMC) in Sophia Antipolis, which he has directed since its inauguration.

While pursuing his scientific career, Michel Lazdunski has devoted a great deal of time to teaching. He became a professor at the University of Marseilles in 1965, and was given the chair of biochemistry of the University of Nice in order to pursue teaching activities and conduct research. Upon the foundation of the Institut universitaire de France in 1991, he was appointed professor at the institute, where he holds the chair in molecular pharmacology.

Over the course of his career, Michel Lazdunski has been a member or chairman of a number of national committees at CNRS, INSERM, and the Ministries of Research and Education. He has also been on a number of scientific boards and the administrative boards of French charities, as well as scientific boards for the organization of European efforts to support biological research (Committee for Life and Health Sciences of the EEC, boards of the European Molecular Biology Organization). He is currently a member of the CNRS Scientific Board, a member of the National committee for the coordination of life sciences, and heads the initiative by the Ministry of Research to create young research teams. In addition, he is on the editorial board of a number of international scientific journals.

Michel Lazdunski received the CNRS Silver Medal in 1976 for his work on enzymology and the structure of proteins. He has received several prestigious awards, such as the Grand Prix of the French Academy of Sciences for biological research (Charles Léopold Mayer Prize) in 1983, the International Society for Cardiac Research Prize in 1984, the Athéna Foundation - Institut de France Prize in 1991, and the Grand Prix of the French Academy of Sciences for research of importance to the medical field. Also in 1991, his team received the Bristol-Myers Foundation Neuroscience Award. Michel Lazdunski is a member of several academies, including the Academia Europaea, which he joined in 1989, and the French Academy of Sciences (1991). He is a foreign correspondent member of the Belgian Royal Academy of Medicine (1991).

He is an officer of the Legion of Honor and the National Order of Merit.

Michel Lazdunski's Research

Michel Lazdunski began his scientific career with the analysis of the properties of the structure of proteins, protein-protein interactions, and the mechanisms of enzymatic catalysis, research for which he was awarded the CNRS Silver Medal. For nearly 25 years, he has devoted the bulk of his research to ion channels. The primary function of ion channels is to act as the microgenerators of biological electricity used by the cells of the nervous system to communicate among themselves and with their target organs, by muscular and vascular cells to trigger contraction, by cardiac cells to control the rhythm of heart contractions, and by the cells of the endocrine system to regulate the secretion of hormones. Ion channels are protein macromolecules located in the cell membranes that enable the selective movement of sodium, potassium, and calcium from outside the cell to inside the cell and vice-versa. They are found in the cells of excitable systems (the nervous, cardio-vascular, and hormonal systems) and in cells that do not generate bioelectricity (kidneys, lungs, immune system, etc.). Here they play a different role—for example, as regulators of the level of sodium in the blood via the kidney cells or the secretion of chloride and, consequently, aqueous fluid by the lung cells.

Michel Lazdunski and his team were pioneers in the exploration of the molecular nature of ion channels and their functioning. They combined experimental approaches to biochemistry, molecular and cell biology, electrophysiology, and pharmacology. First, they built up an arsenal of toxins extracted from the poison of scorpions, sea anemones, snakes, bees, spiders, planktonic algae, and plants. Many of these substances are used all over the world today as tools for the investigation of the nervous, cardio-vascular, and muscular systems. These toxins served as probes for the identification, purification, and analysis of the workings of the ion channels that are their targets. In addition, they provide models for the study of muscular diseases, cardiac arrhythmia, epileptic seizures, and insomnia. Very weak concentrations of some of these substances can, for example, stimulate learning and memory. When applied to insects, others of them have insecticide properties.

A wide range of drugs also targets ion channels. Michel Lazdunski's team has played a critical role in the analysis of how calcium channel blockers work. This major class of drugs is used to treat high blood pressure. The team also demonstrated that sulfonylureas, a class of drugs taken by millions of people with diabetes, target a particular class of potassium-permeable channels in the pancreatic cells that secrete insulin; prior to this, scientists did not have a clear understanding of sulfonylureas' mechanism of action. The nervous system has a multitude of other types of potassium-permeable channels, which give each type of neuron its electrical character. Michel Lazdunski and his group recently identified a new class of potassium channels that play a central role in the control of the resting potential of the nerve cells of the brain and spinal cord; they are present in the neurons associated with the memorization process and those involved in motor activities. By demonstrating that this class of channels is the target of volatile general anesthetics, Michel Lazdunski and his research team elucidated a mystery dating back 150 years to the introduction of ether and chloroform. By stimulating the activity of this new class of ion channels, volatile general anesthetics hyperpolarize the nerve cells and slow communications between the neurons by the neurotransmitters. The team's discovery could contribute to the development of new, safer, and more effective anesthetic agents. This new class of ion channels is also the target of powerful neuroprotective molecules with potential applications to treat retinal ischemia, often caused by glaucoma; to treat ischemia of the spinal cord leading to paraplegia; and to treat cerebral ischemia leading to rapid neuron death, especially in the structures that control short term memory.

Michel Lazdunski and his colleagues at the CNRS Institute of Molecular and Cell Pharmacolocy have also conducted extensive research on potassium-permeable channels, which are essential for the functioning of the heart. In particular, his research team has identified the structure and functioning of a new channel that is crucial to maintaining a normal heart rhythm. The mutation of this channel leads to long QT syndrome and arrhythmias in tachycardias, resulting in syncopes and sudden death. This same channel is expressed in the inner ear. The ablation of one of the genes that codes for this channel or the appearance of certain mutations can result in both heart disease and deafness. Two potential therapeutic applications stem from this type of research: the difficult task of identifying new types of anti-arrhythmics to act on a target that has now been clearly identified; and the identification of the effects of arrhythmias produced as a side effect of various drugs used for other diseases.

Ion channels are also essential for sensory perception, including taste, mechanical perceptions (sense of touch), hot and cold, and the perception of pain. Michel Lazdunski and his team identified, at the molecular level, the ion channels that convert a mechanical stimulation into an electrical signal. They also identified a class of channels commonly expressed in nociceptors, which are sensory cells specialized in the perception of pain. Nociceptors are activated by extracellular acidosis produced in cases of inflammation, hematomas, cardiac ischemia, muscle cramps, and certain tumors. This new type of channel, which responds to acidic stimulation, enables an electrical signal to be generated, traveling from the sensory endings to the spinal cord and the regions of the brain that govern the sensation of pain.

The ion channels of non-excitable tissues have also been studied by Michel Lazdunski and his team, who isolated genes associated with a renal ion channel that allows the transit of sodium and plays a key role in the regulation of the sodium concentration in the blood. This is an important factor in a common condition, high blood pressure. His team has made a significant contribution to the analysis of a channel that transports the ion chloride, which is mutated in patients with cystic fibrosis. In particular, the researchers discovered the first molecule capable of activating this pulmonary ion channel, whose activity is diminished or practically destroyed by the disease. They thus opened a potential avenue of therapeutic research to find new drugs.

In a nutshell, over the last 25 years, Michel Lazdunski and his team have not only elucidated the molecular properties of the structure and functioning of ion channels; in addition, using a highly diverse and sophisticated pharmacological arsenal, they shed new light on the role of these ion channels and other ion transport systems in a wide range of diseases, including high blood pressure, abnormal heart rhythms, cardiac insufficiency, cerebral ischemia and ischemia of the spinal cord, epilepsy, muscle diseases, diabetes, cystic fibrosis, and retinal disorders due to glaucoma, etc. With such far-reaching accomplishments to their name, Michel Lazdunski and his colleagues are the international specialists of ion channels and their pharmacology.

Department of Life Sciences Contact:
Thierry Pilorge
Tel : 33 1 44 96 40 26
e-Mail: thierry.pilorge@cnrs-dir.fr

Researcher Contact:
Michel Lazdunski, directeur de l'IPMC
Tel : 33 4 93 95 77 03
e-Mail : lazdunski@ipmc.cnrs.fr

Press Contact:
Martine Hasler
Tel: 33 1 44 96 46 35
e-Mail : martine.hasler@cnrs-dir.fr