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Protein controls acid in cells by direct detection of volume changes, study finds

ium is a major mechanism of cell death in ischemic episodes. Virtually every study that has been done (on inhibiting NHE1) has shown that if you block this transporter, you can prevent this type of cell death from ischemia."

Previous studies have suggested that NHE1 plays a role in cancer cells that are trying to spread, or metastasize, to different parts of the body. As cancer cells move, they must change their volume, protruding at one end and retracting on the other. Dr. Hilgemann said other researchers speculate that NHE1 is at the head of the cell as it is moving, and is always rearranging itself to be at the cell's head.

"While the cancer applications are very speculative, understanding this system can be very important for many aspects of cell biology," he said.

The new study also compares NHE1 to another, very similar transporter called NHE3, which is found only in the kidneys.

"We found there are very specific differences in the way these two systems respond to changes in the cell," Dr. Hilgemann said. "For example, the one in the kidney is involved in reabsorbing sodium, but it is not regulated at all by changes in cell volume."

Dr. Hilgemann and his colleagues improved upon an existing experimental technique in order to study the NHE transporters and how acidity changes within a cell. The existing method involves skewering a single cell on a tiny, hollow needle called a pipette. Dr. Hilgemann's group made their pipette larger to make a larger hole in the cell, which allowed them better control over what was inside and outside of the cell.

They also optimized the use of tiny sensors that can measure exactly the movement of protons across the cell membrane. "This tells us how the acidity is changing," Dr. Hilgemann said. "Our advancements allow us to better show and study how these systems are working."

Other UT Southwestern researchers who contributed to the study are Dr. Daniel Fuster, a postdoctor
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Contact: Amanda Siegfried
amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
5-Jul-2004


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