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Structural studies reveal how potassium channels are inactivated

Researchers have discovered how potassium channels can slam shut, a control mechanism that allows neurons to regulate their firing frequency.

Using techniques to produce precise mutations in the channels, the researchers then used x-ray crystallography to deduce that one of four long tails, called inactivation gates, at the end of the channel can slide into the channels pore and shut it down. The studies not only settle the question of how potassium channels manage to close milliseconds after opening, but also offer new insights that will aid in designing drugs that control the channels more precisely.

The research team, led by Howard Hughes Medical Institute investigator Roderick MacKinnon at The Rockefeller University, published its findings in the June 7, 2001, issue of the journal Nature.

To maintain the correct concentration of potassium, cells are equipped with potassium ion channels, pore-like proteins that poke through the cell membrane. These channels create sieves through which potassium ions flow from inside to outside the cell. Moving potassium through the cell membrane is critical to numerous life-sustaining functions, including the beating of the heart, insulin release in response to changes in blood sugar, and nerve signal generation. When a nerve signal travels the length of a neuron, for example, large amounts of potassium must be able to flow quickly from the inside to the outside of a cell. This outflow of potassium allows the membrane to return to its resting state and prepare for the next impulse.

Structural studies conducted during the last three years showed that the channels are composed of four identical subunits that fit together to form a cone-shaped pore that spans the cell membrane.

In earlier studies, MacKinnon and his colleagues reported that potassium channels have side openings that are located above a p
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
6-Jun-2001


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