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.
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