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Solving the puzzle of the BK ion channel
Date:6/23/2010

In 2004, Washington University in St. Lous researcher Jianmin Cui was handed a puzzling clue to the structure of an ion channel his lab had been studying for five years.

Scientists at the Cleveland Clinic Foundation in Ohio had located a large family whose members suffered from epilepsy, sudden attacks of involuntary movement or both, a syndrome called generalized epilepsy and paroxysmal dyskinesia (GEPD).

By analyzing the DNA of the 16 family members who had inherited the syndrome, the Cleveland Clinic scientists identified a mutation in the study family in the gene that encodes the big-conductance potassium ion channel (also known as the BK or MaxiK channel). This was one of the ion channels Cui, PhD, the Spencer T. Olin Associate Professor of Biomedical Engineering in the School of Engineering & Applied Science, had long studied.

Ion channels are small, highly selective pores in the cell membrane that allow specific ions (charged atoms) to enter or leave the cell. They are not continuously open but instead have gates, which open briefly and then close again in response to electrical, mechanical or chemical signals.

The mutation changes a single amino acid, or protein building block, in the BK channel.

The scientists thought that the mutation led to an increase in channel activity and thus nerve-cell excitability, causing epilepsy or involuntary movement, depending on which parts of the central nervous system were affected by the mutation.

But there was a problem. The altered amino acid was not part of the gate that opens and closes the channel.

Cui and his colleagues were thus faced with the problem of action at a distance. How did the mutation that apparently didn't interfere with the channel's gate nevertheless alter how often it was open?

Meticulous work that involved mutating other amino acids and testing the electrical properties of the mutated channels in frog eggs finally led to
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Contact: Diana Lutz
dlutz@wustl.edu
314-935-5272
Washington University in St. Louis
Source:Eurekalert  

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