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Researchers discover structure of Nature's 'circuit breaker'

Researchers have answered an important question in biology by discovering the exquisite mechanism by which channels in the cell membrane sense voltage changes that trigger them to snap open or slam shut with extraordinary speed and precision.

Voltage-dependent ion channels are central to the function of nerves and muscles, and without them the brain would immediately suffer neural gridlock and the heart would seize up.

According to the researchers, which were led by Howard Hughes Medical Institute investigator Roderick MacKinnon, the discovery may lead to a new class of drugs for neurological, heart and muscle disorders that can exert more subtle influences on the activity of ion channels.

MacKinnon and his colleagues at The Rockefeller University published their findings in two papers in the May 1, 2003, issue of the journal Nature. Specifically, the researchers deduced the structure and function of the voltage-sensing mechanism in a potassium channel of an archaebacterium that thrives in the near-boiling temperatures of hot springs. However, they said, the mechanism undoubtedly applies to voltage-sensing calcium and sodium channels as well, and is present in organisms from the most ancient bacteria to humans.

Voltage-dependent potassium ion channels are precise molecular machines that are critical to propagating electrical impulses in the brain and heart. The channels are large proteins with a pore that pierces the cell membrane and is designed to allow only the passage of potassium ions. When an electrical impulse travels along a nerve, the charge on the cell membrane changes -- with the outside becoming more negative -- triggering these ion channels to open and allowing potassium to flow out of the cell. This outflow of potassium allows the membrane to return to its resting state and prepare for the next impulse.

According to MacKinnon -- whose pa
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
30-Apr-2003


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