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Learn MorePiezo1 is a mechanosensitive (MS) ion channel with characteristic fast-inactivation kinetics expressed in multiple mammalian cells. We found a slowly-inactivating MS current in mouse embryonic stem (mES) cells and characterized it throughout a model differentiation into motor neurons in order to investigate its components. MS currents were large and slowly-inactivating in the stem cell stage, and became gradually smaller and faster-inactivating throughout the differentiation. We found that Piezo1 is expressed in mES cells, and its knockout abolishes MS currents, indicating that the slowly-inactivating current in mES cells is carried by Piezo1. To investigate the reason for its uncharacteristic slow inactivation kinetics in these cells, we cloned Piezo1 cDNA from mES cells and studied whether the expressed variant displays intrinsic slow kinetics. The variant of Piezo1 found in mES cells displays fast-inactivation kinetics in heterologous expression, indicating that sources of modulation other than the amino acid sequence determine its slow kinetics in mES cells. SOURCE: Josefina,Inés,del Mármol (jdelmarmol@rockefeller.edu) - The Rockefeller University
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