2004 Stetten Lecture Ion Channels: Life's Electronic Hardware Wednesday, October 27, 2004 3:00 - 4:00 p.m. Masur Auditorium Warren Grant Magnuson Clinical Center (Building 10) National Institutes of Health Speaker: Roderick MacKinnon, M.D. Professor, Laboratory of Molecular Neurobiology and Biophysics Investigator, Howard Hughes Medical Institute Rockefeller University

Biographical Sketch

Cells don’t let just anything slip past their external membranes. Instead, protein channels control the passage of most substances, including the ions that allow nerves to signal, muscles to flex, and hormones to be secreted in an orderly way. For more than a century, chemists have understood that the flow of ions across membranes could produce electrical signals. But exactly how ion channels work has become clear only since 1998, when Roderick MacKinnon, M.D., showed for the first time what these proteins look like at the atomic level. This was such a fundamental achievement that he received the Nobel Prize in chemistry just five years later.

MacKinnon has now solved several riddles about the way ion channels operate, such as how they so precisely limit the types of ions that pass through, why they sometimes conduct ions in one direction only, and how these cellular gates open and shut under different conditions. To answer these questions, MacKinnon has trapped ion channel structures in action. He has shown, for example, that the arrangement of oxygen atoms lining a channel’s pore allows the specific capture of potassium ions and the exclusion of smaller sodium ions. He has also shown that ions can pass through the channels about as fast as they would flow if unimpeded by any membrane because changes in channel configuration are remarkably well balanced energetically. Sensors built into the channels can open and close them in response to changes in ion concentrations, voltage, or the binding of small molecules.

In addition to solving fundamental puzzles about an essential part of all cells, MacKinnon’s work has opened new targets for the pharmaceutical industry. Some serious diseases, including disorders of the nervous system and heart, stem from disturbances in ion channel function.

MacKinnon heads the Laboratory of Molecular Neurobiology and Biophysics at Rockefeller University in New York City, 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, he began research on ion channels. He was a professor at Harvard Medical School between 1989 and 1996. In addition to the Nobel Prize in 2003, MacKinnon’s many 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.