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 toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Older 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.

中文翻译：

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机械敏感的PIEZO通道的电压门控。

机械敏感的PIEZO离子通道是进化保守的蛋白质，其存在对于多细胞生物的正常生理至关重要。在这里，我们表明，除了机械刺激之外，PIEZO通道还可以通过电压进行强大的调制，甚至可以切换到纯电压门控模式。导致诸如干细胞增多症等人类疾病的突变，使PIEZO1通道的电压敏感性朝着静止的膜电位转移，并极大地促进了电压门控。可以通过孔中存在失活栅极来解释电压调制，该失活栅极的开口通过向外渗透而促进。较老的无脊椎动物（苍蝇）和脊椎动物（鱼类）的PIEZO蛋白也对电压敏感，但是电压门控是这些较老通道的更显着特征。