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Atomic structure discovered for a sodium channel that generates electrical signals in living cells
Date:7/13/2011

ntists more about the biomechanics of a voltage-gated sodium channel.

"We hope to gain insight into why they selectively let in sodium ions and nothing else," the researchers said, "and how they respond to changes in the cell membrane voltage, how they open and close, and how they generate electrical signals." The researchers have already spotted intriguing molecular movement, such as rolling motions of some functional parts of the sodium channel molecule and their connectors.

Knowing how form affects function in sodium channels could lead to many new ideas from scientists around the world on designing drugs to home in on critical areas of the sodium channel molecule. The implications for drug therapies are enormous.

For example, the authors of the Nature paper unexpectedly discovered a portal large enough for small pore-blocking drugs to enter the central cavity of the sodium channel.

"There is a lot of interest in drug design based on the structure of this molecule and its binding sites," Catterall said. "Scientists hope to discover better drugs that exert their effects on specific targets within the sodium channel. In particular, they want to find better pain medications with fewer side effects and improved treatments for seizure disorders and heart rhythm problems, such as those leading to sudden cardiac death."

In 1980 Catterall identified ion channel molecules for the first time by locating the protein subunits of the sodium channel. Earlier, in the 1970s, his UW colleague Dr. Bertil Hille, professor of physiology and biophysics, had analyzed the electrical signals produced by ion channels and had proposed mechanistic models for their function.

The new structure reveals how the mechanistic models that Hille proposed work in three dimensions.

After more than 30 years of studying sodium ion channels, Catterall said the ability to visualize the subject of his life-long research in incredibly d
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Contact: Leila Gray
leilag@u.washington.edu
206-685-0381
University of Washington
Source:Eurekalert

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