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Archive - Mar 9, 2013

Genetic Defect Affecting Mechanosensitive Ion Channel Is Cause of a Hereditary Anemia

A genetic mutation that alters the kinetics of an ion channel in red blood cells has been identified as the cause of a hereditary anemia, according to a paper published online on March 4, 2013 in PNAS by University at Buffalo (UB) scientists and colleagues. The research team was led by Frederick Sachs, Ph.D., State University of New York Distinguished Professor in the UB Department of Physiology and Biophysics, who discovered in the 1980s that some ion channels are mechanosensitive, that is, they convert mechanical stress into electrical or biochemical signals. The findings of the new study are significant, Dr. Sachs says, because it is the first time that defects in a mechanosensitive ion channel have been implicated as the cause of a disease. “We found that the mutations in the gene that codes for the ion channel called PIEZO1 causes the channel to stay open too long, causing an ion leak in red cells,” explains Dr. Sachs. “Calcium and sodium enter, and potassium leaves, and that affects the ability of the red cell to regulate its volume. The cells become dehydrated and can break open, releasing their hemoglobin into the blood, and causing symptoms, such as the shortness of breath seen in anemic patients.” The anemia that results from the mutations in PIEZO1 is called familial xerocytosis, a mild to moderate form of anemia. The ion channel, PIEZO1, is about 10 nanometers across, and it increases its dimensions significantly upon opening; that change in dimensions is what is responsible for its mechanical sensitivity. Mechanosensitive ion channels are likely to play a role in many diseases, because all cells are mechanically sensitive. Dr.

Temperature-Controlled Nanopores May Enable Detailed Blood Analysis

Tiny biomolecular chambers called nanopores that can be selectively heated may help doctors diagnose disease more effectively if recent research by a team at the National Institute of Standards and Technology (NIST), Wheaton College, and Virginia Commonwealth University (VCU) proves effective. Though the findings may be years away from application in the clinic, they may one day improve doctors' ability to search the bloodstream quickly for indicators of disease—a longstanding goal of medical research. The work was published online on January 24, 2013 in the Journal of the American Chemical Society. The team has pioneered work on the use of nanopores—tiny chambers that mimic the ion channels in the membranes of cells—for the detection and identification of a wide range of molecules, including DNA. Ion channels are the gateways by which the cell admits and expels materials like proteins, ions, and nucleic acids. The typical ion channel is so small that only one molecule can fit inside at a time. Previously, team members inserted a nanopore into an artificial cell membrane, which they placed between two electrodes. With this setup, they could drive individual molecules into the nanopore and trap them there for a few milliseconds, enough to explore some of their physical characteristics. "A single molecule creates a marked change in current that flows through the pore, which allows us to measure the molecule's mass and electrical charge with high accuracy," says Dr. Joseph Reiner, a physicist at VCU who previously worked at NIST. "This enables discrimination between different molecules at high resolution.