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Structure of Potassium Channel Solved
6 April 1998 7:30 pm
Scientists have worked out the structure of the potassium ion channel, a sluice in the cell membrane that enables neurons to transmit electrical signals. The accomplishment, reported in the current Science, may provide a blueprint for designing drugs to treat ailing nerve cells.
Every nerve signal, from the thoughts in your head to those that control your heartbeat, depends on a voltage spike. When the neuron gets a cue, gates on sodium channels are thrown open, ions rush in, and the voltage surges. For more than 50 years, scientists knew that the background voltage is maintained by other channels, which allow only potassium to slowly leak out. A step forward came in 1995, when scientists deciphered the genetic sequence for a potassium channel from the bacteria Streptomyces lividans. This enabled biophysicist Roderick MacKinnon and colleagues at Rockefeller University to mass produce the pore protein and probe its crystal structure with x-rays.
The team found that the channel sits in the cell membrane like a flower with its petals opening to the outside of the cell. Although any kind of ion can enter the long hollow stem--the pore of the channel--only potassium ions can pass through a filter near the pore's end. That's because sequential rings of oxygen atoms exactly match the size, and balance the charge, of potassium ions. What's more, the ions don't dawdle as they march single file through the filter: as each potassium ion enters, its charge repels the ion ahead, pushing it out the channel. Potassium channels in human cells most likely work the same way, the researchers say. In an accompanying paper, MacKinnon's team notes that scorpion toxin--a potent potassium channel inhibitor--has the same effect on pores in S. lividans and those of the fruit fly Drosophila, whose nuclei are organized similar to those of human cells.
The two papers hint at "many pharmacological applications," says University of Pennsylvania biophysicist Clay Armstrong. Potassium channels are important in irregular heartbeats and diseases such as adult onset diabetes, he notes, and understanding exactly what they look like improves the ability to design drugs for treatment.