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Nobelist To Give Stetten Lecture On Ion Channels, Oct. 27

By Karen Jegalian

The body uses electrical currents to translate light into sight, relay information from nerve to nerve, coordinate the pumping of the heart and allow actions as fine as threading a needle and as powerful as sprinting. The controlled flow of currents, for these uses and many others, depends on ion channels, which permit charged particles to pass through cell membranes.

Dr. Roderick MacKinnon of Rockefeller University has been studying ion channels for the past 18 years. Since 1998, his research group has determined the atomic structures and mechanism of action of several ion channels. Last year, he received the Nobel Prize in chemistry for his discoveries.

Dr. Roderick MacKinnon
MacKinnon will describe recent findings about how these portals control what passes through them in this year's DeWitt Stetten, Jr., Lecture, titled, "Ion Channels: Life's Electronic Hardware." The talk, part of the NIH Director's Wednesday Afternoon Lecture Series and sponsored by NIGMS, will be held on Oct. 27 at 3 p.m. in Masur Auditorium, Bldg. 10.

According to NIGMS director Dr. Jeremy Berg, MacKinnon "has done whatever was needed to find out the structure and function of ion channels. As an M.D., he realized how fundamental these channels are to medicine. He's a problem-driven, determined, focused scientist who wasn't limited by what he was originally trained to do."

MacKinnon first became interested in ion channels when he was completing a residency in internal medicine at Beth Israel Hospital in Boston. He started attending weekly meetings held by ion channel researchers and visited their labs, where he saw that they could observe single channels in real time and track conformational changes as they happened.

"It was somewhat serendipitous that I became interested in ion channels," MacKinnon said, "but I kept having a yearning to pursue basic science. During my residency, I decided I had no choice but to become a scientist."

MacKinnon was attracted to the quantitative rigor of studying ion channels and in particular to two issues: channel discrimination and gating. He wondered exactly how, for example, a potassium channel permits the rapid passage of large numbers of potassium ions while excluding similar, but smaller, sodium ions. He's also still trying to understand the controlled opening and closing of ion channels, particularly in response to voltage changes.

MacKinnon made a bold decision in the mid-1990's. At the time, the way to study ion channels was to introduce mutations into them and then measure the resulting channels' electrical activity, testing whether the changes affected ion conduction. MacKinnon decided that to really understand how channels worked, he would have to see them. And to see them, he needed a crystal structure. This was a daring approach because membrane proteins are notoriously difficult to crystallize, especially large ones such as ion channels.

MacKinnon taught himself X-ray crystallography and devoted his research group to the task of figuring out a channel's atomic structure. Remarkably, his group had its first crystal structure in less than 2 years.

Pharmaceutical companies are interested in ion channels as targets for drugs to treat diseases ranging from cardiac arrhythmias to cystic fibrosis. Disorders of ion transport also affect the kidneys, nervous system and endocrine system.

MacKinnon heads the laboratory of molecular neurobiology and biophysics at Rockefeller, where he has been a professor since 1996. He is also an investigator of the Howard Hughes Medical Institute. MacKinnon received a B.A. in biochemistry in 1978 from Brandeis University and an M.D. in 1982 from Tufts University. After completing a medical residency followed by a postdoctoral fellowship with Christopher Miller at Brandeis, he was a professor at Harvard Medical School from 1989 to 1996. In addition to the Nobel Prize in 2003, MacKinnon's honors include the 1999 Albert Lasker Basic Medical Research Award and election to the National Academy of Sciences in 2000.

NIGMS has supported MacKinnon's research since 1990.

For more information or for reasonable accommodation, call Hilda Madine at (301) 594-5595.

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