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February 25, 2000
PUMPING IONS: MBL Scientists Study Nerve Cells of Squid to Learn More About a Crucial Cellular Machine

Woods Hole, MA - Even when you're sound asleep, the billions of cells that make up your body are hard at work. They send messages, transport nutrients, and maintain strategic gradients of important chemicals, among a myriad of other vital functions. In short, your cells’ hard work helps keep you healthy—and alive.

At rest, about half of your body’s energy consumption is used for pumping ions—electrically charged chemicals like sodium and potassium—across the surface membrane of cells. Cells do this to maintain important chemical gradients within your body. Those gradients are a form of currency that the cells spend to accomplish many crucial jobs. One cell can contain millions of ion pumps, which function with astonishing efficiency. A single cell can move millions of ions in under a second. If your cells can’t adequately transport these ions, they cannot maintain vital ion gradients, putting you at risk for heart disease, stroke, or even death.

Because the sodium/potassium pump is essential to the health of virtually every cell in all animals, including humans, scientists at the Marine Biological Laboratory in Woods Hole have spent years studying the molecular mechanisms by which this pump transports sodium and potassium ions across cellular membranes. They use the giant nerve cell of the Woods Hole squid (Loligo pealeii) as a model system for their research.

This week in the journal Nature Miguel Holmgren and his colleagues, all summer investigators at the Marine Biological Laboratory (see home affiliations below), describe their latest findings about how this microscopic molecular machine, the sodium/potassium exchange pump, actually works. They already knew that this pump, which is a single protein molecule, transports three sodium ions across the cell membrane at once. But they have now shown that three separate changes in the shape of the pump protein release the three sodium ions from the pump one at a time, in a fixed sequence. This new information will help scientists understand in greater detail how these, and other, essential ion pumps perform the crucial work that keeps all our cells alive.

For more than sixty years, the Woods Hole squid's giant nerve cell has helped scientists answer many basic questions about how electrical signals are generated in a nerve cell, and how they travel along the nerve axon and are then transmitted from nerve cell to nerve cell; how nutrients and other important particles are transported from one end of a long nerve cell to another; and how certain cells maintain the body's pH level. Scientists use squid axons because they are unusually large—about a thousand times wider than their counterparts in humans—and are therefore more easily manipulated for study. Basic research on the squid has provided researchers and clinicians with vital information that has helped them develop a better understanding of such debilitating human diseases as heart disease, stroke, cancer, Alzheimer's Disease, and kidney disease.

Every spring, tens of thousands of Woods Hole squid begin their migration to the waters off Cape Cod. They come to the shores of Woods Hole like clockwork, like the swallows to San Juan Capistrano.

Soon after the waters off Woods Hole teem with squid and fishing boats, the laboratories of the Marine Biological Laboratory Whitman building begin to bustle with scores of neurobiologists, like the authors of this week’s Nature paper. These scientists follow the squid to Woods Hole each year. They come to the MBL every spring and summer from universities and medical schools as close as New York and Boston and as far away as Germany and Argentina. The researchers spend night and day in the laboratory, using the Woods Hole squid as a model for understanding basic neurobiological processes, like how ion channels and sodium pumps work.

The Marine Biological Laboratory is an independent scientific institution, founded in 1888, that undertakes the highest level of creative research and education in biology, including the biomedical and environmental sciences.

Holmgren, Miguel, Jonathan Wagg, Francisco Bezanilla, Robert F. Rakowski, Paul De Weer, and David C. Gadsby. 2000. Three distinct and sequential steps in the release of sodium ions by the Na+/K+ ATPase. Nature. 403: 898-901.

Miguel Holmgren, Harvard Medical School
Jonathan Wagg, rSafe Inc., San Francisco
Francisco Bezanilla, UCLA
Robert F. Rakowski, Finch University of Health Sciences/Chicago Medical School
Paul De Weer, University of Pennsylvania
David C. Gadsby, The Rockefeller University