Discovering How Cell 'Doors' Open and Close

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Kirstie Saltsman

Cells don't let just any substance slip through their protective external membranes. Most substances must first convince cells to open their doors to allow them in or out. Scientists have known for years that electrically charged particles, such as sodium and potassium ions, can pass across a cell's membrane through tunnel-like protein structures known as ion channels. Ion channels are critical to many biological processes, such as the beating of the heart, nerve impulses, digestion, and insulin release. But until recently, the precise mechanisms by which cells open and close these doors to the outside world have largely remained a mystery.

In a continuation of his Nobel Prize-winning ion channel research, Roderick MacKinnon has recently determined the three-dimensional structure of a "voltage-dependent" potassium channel. His findings have challenged the previously accepted view of how these channels sense voltage changes across the cell membrane. The segment of the channel that acts as the sensor turns out to extend into the membrane itself rather than being tucked in on the inner surface of the channel, as had been believed. The sensor is pulled from one side of the membrane to the other when the voltage changes. In turn—through a process not yet understood—the sensor pulls on other parts of the channel, causing it either to open or close. The sensor thus responds to voltage changes much like the button of an automatic door responds to pressure: It senses the stimulus and brings about a response.

Nigel Unwin, Ph.D., a cell biologist at The Scripps Research Institute in La Jolla, California, has been studying a different type of ion channel: one that responds to a chemical, rather than an electrical, stimulus. He has found that this channel, called the acetylcholine receptor, has door-like segments in its middle that, when closed, block the flow of ions. The doors are attached to the rest of the channel through hinge-like regions around which they can rotate. When the chemical messenger binds to the channel, the doors open, allowing ions to pass through.

A deeper understanding of the workings of ion channels may allow scientists to develop new drugs for conditions ranging from heart disease to diabetes.