Voltage gating of mechanosensitive PIEZO channels

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Item Type:

Article

Title:

Voltage gating of mechanosensitive PIEZO channels

Creators Name:

Moroni, M. and Servin-Vences, M.R. and Fleischer, R. and Sánchez-Carranza, O. and Lewin, G.R.

Abstract:

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.

Keywords:

Ion Channels in the Nervous System, Ion Transport, Mechanisms of Disease, Peripheral Vascular Disease, Permeation and Transport, Animals, Drosophila, Zebrafish, Mice

Source:

Nature Communications

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Volume:

Number:

Page Range:

1096

Date:

15 March 2018