TY - JOUR T1 - Voltage-gating of mechanosensitive PIEZO channels JF - bioRxiv DO - 10.1101/156489 SP - 156489 AU - Mirko Moroni AU - Martha Rocio Servin-Vences AU - Raluca Fleischer AU - Gary R. Lewin Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/27/156489.abstract N2 - Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage gated mode. Mutations that cause human diseases such as Xerocytosis profoundly shift voltage sensitivity of PIEZO1 channels towards the resting membrane potential and strongly promote pure voltage gating. Our data may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts. ER -