Why a hereditary anaemia is caused by genetic mutation in mechanically sensitive ion channel

A genetic mutation that alters the kinetics of an ion channel in red blood cells has been identified as the cause behind a hereditary anaemia.
The research team was led by Frederick Sachs, PhD, SUNY Distinguished Professor in the UB Department of Physiology and Biophysics, who discovered in the 1980s that some ion channels are mechano-sensitive, that is, they convert mechanical stress into electrical or biochemical signals.
The findings of the new study are significant, Sachs says, because it is the first time defects in a mechano-sensitive 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 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 haemoglobin into the blood, and causing symptoms, such as the shortness of breath seen in anaemic patients.’
The anaemia that results from the mutations in PIEZO1 is called familial xerocytosis, a mild to moderate form of anaemia. 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.
Mechano-sensitive ion channels are likely to play a role in many diseases, since all cells are mechanically sensitive. Sachs and his colleagues have worked on activation of these channels in Duchenne muscular dystrophy, which is caused by errors in a gene coding for a fibrous protein that reinforces the cell membrane. The increased stress caused by this loss of reinforcement causes the channels to open and the leak of calcium is likely what causes the muscles to atrophy, Sachs explains. University at Buffalo