A cell door that automatically snaps shut in milliseconds - this isn't
the latest jailbreak deterrent but a fundamental part of our cells. Nearly 50
years after this microscopic marvel was discovered, researchers in New York
have dissected the inner workings of the molecule responsible for generating
the body's electrical impulses
All excitable cells - such as those responsible for nerve signals, muscle contraction or the heart beat - depend on ion channels in the cell membrane. Triggered to open by a small voltage, such channels let through a flood of electrically charged ions, then promptly slam shut.
The 'ball-and-chain' model was put forward in the 1970s to explain how this 'inactivation' occurs. The model suggested that a plug - or ball - swinging on a molecular 'chain' on the inside of the channel stops up the opening. Now Roderick MacKinnon and his colleagues at Rockefeller University in New York have found that the ball is more like a snake that sneaks inside the channel to block it.
"The wall of the pore is greasy," explains MacKinnon, and the ball slips right through the channel to fit snugly into a cavity in the centre. The team systematically altered the building blocks of a bacterial ion channel to discover which bits controlled its function.
Small molecules that mimic the plug also fit the same niche, the group found, which may raise their profile as potential drug targets. Agents targeting ion channels are already used as anaesthetics and to control irregular heart beat. Says MacKinnon: "There is a sense that people are appreciating these molecules."
For cell physiologists such as Richard Aldrich of Stanford University in California, the affair with ion channels is already decades old. Fifty years ago, it was realized that nerve impulses were created by the cell membrane allowing ions in and out of the cell - neuroscientists have been working on the mechanism ever since. "Essentially this unifies all the results across the years," says Aldrich. "It finally ends the story."
Working out the three-dimensional structure of ion channels is technically testing - they must be washed out of oily cell membranes by means of detergent, and collecting enough protein for the analysis is very time-consuming. By modifying bacteria to churn out large numbers of the channels, MacKinnon's team finally managed to solve its structure. Similar potassium-ion channels control the rate at which nerve cells fire in the brain.
Now ion-channel addicts are trying to crack the complete structure of a voltage-sensitive ion channel in mammals. "That's what keeps me coming into work in the mornings," says MacKinnon. "It will be a marvellous mechanism."