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New protein senses salt balance in vertebrates
  
By Bijal P. Trivedi

Researchers have identified the first vertebrate gene that senses the body's total salt balance, which affects the size and shape of a cell. The gene, VR-OAC (Vanilloid Receptor-Related Osmotically Activated Channel), has been found in humans, mice, rats, and chickens. The finding could have major implications for the development of new diuretic and some antihypertensive drugs that work by regulating the salt balance.

Osmotic pressure, or total salt balance, is the most tightly controlled parameter in the body, says Jeffrey Friedman, of The Rockefeller University in New York City. "Cells don't like to be too big or too small and the salt level is critical to maintaining the size and shape of every cell in the body," says Friedman.

If the salt level in the body were not carefully regulated, water would rush into the cells, causing them to swell and possibly burst.

In yeast and bacteria, single-celled creatures, proteins in the membrane regulate the balance of salt and water inside of the cell. In more complicated creatures, the brain takes the job of regulating salt and water balance for the whole organism. In humans VR-OAC is found in the cell membrane of brain, kidney and inner ear cells.

Wolfgang Liedtke, who led the research at Rockefeller, discovered VR-OAC while hunting for genes that are sensitive to body temperature. Liedtke used the heat sensitive vanilloid receptor gene as "bait" to fish out similar genes from the hypothalamus—the region of the brain that regulates body temperature, hunger, body weight, sleep, and thirst. He pulled out VR-OAC, a gene that looks similar to the vanilloid receptor but is sensitive to salt concentration rather than heat. Liedtke's report appears in a recent issue of Cell.

The VR-OAC protein is nestled in the membrane of cells in the hypothalamus and alters the flow of calcium in and out of the cell continuously sensing the body's total salt balance and adapting to changes in its environment. Friedman speculates that when the body's salt level drops, water begins to enter the hypothalamus cells causing them to swell. The membrane then becomes taut stretching open the protein channel. When calcium enters the cell, it triggers chemical reactions that are converted into electrical signals to other regions of the brain telling the body to increase water or salt intake.

What role VR-OAC plays in the inner ear is not understood, says Friedman.

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Liedtke, W. et al. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 103, 525-535 (October 27, 2000).
 

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