Piezo1 ion channels inherently function as independent mechanotransducers

Piezo1 is a mechanically activated ion channel involved in sensing forces in various cell types and tissues. Cryo-electron microscopy has revealed that the Piezo1 structure is bowl-shaped and capable of inducing membrane curvature via its extended footprint, which indirectly suggests that Piezo1 ion...

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Main Authors: Amanda H Lewis, Jörg Grandl
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-10-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/70988
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author Amanda H Lewis
Jörg Grandl
author_facet Amanda H Lewis
Jörg Grandl
author_sort Amanda H Lewis
collection DOAJ
description Piezo1 is a mechanically activated ion channel involved in sensing forces in various cell types and tissues. Cryo-electron microscopy has revealed that the Piezo1 structure is bowl-shaped and capable of inducing membrane curvature via its extended footprint, which indirectly suggests that Piezo1 ion channels may bias each other’s spatial distribution and interact functionally. Here, we use cell-attached patch-clamp electrophysiology and pressure-clamp stimulation to functionally examine large numbers of membrane patches from cells expressing Piezo1 endogenously at low levels and cells overexpressing Piezo1 at high levels. Our data, together with stochastic simulations of Piezo1 spatial distributions, show that both at endogenous densities (1–2 channels/μm2), and at non-physiological densities (10–100 channels/μm2) predicted to cause substantial footprint overlap, Piezo1 density has no effect on its pressure sensitivity or open probability in the nominal absence of membrane tension. The results suggest that Piezo channels, at densities likely to be physiologically relevant, inherently behave as independent mechanotransducers. We propose that this property is essential for cells to transduce forces homogeneously across the entire cell membrane.
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spelling doaj.art-f343575b600542c9bae2202c73b9b8402022-12-22T03:52:50ZengeLife Sciences Publications LtdeLife2050-084X2021-10-011010.7554/eLife.70988Piezo1 ion channels inherently function as independent mechanotransducersAmanda H Lewis0https://orcid.org/0000-0001-7316-9729Jörg Grandl1https://orcid.org/0000-0001-7179-7609Department of Neurobiology, Duke University Medical Center, Durham, United StatesDepartment of Neurobiology, Duke University Medical Center, Durham, United StatesPiezo1 is a mechanically activated ion channel involved in sensing forces in various cell types and tissues. Cryo-electron microscopy has revealed that the Piezo1 structure is bowl-shaped and capable of inducing membrane curvature via its extended footprint, which indirectly suggests that Piezo1 ion channels may bias each other’s spatial distribution and interact functionally. Here, we use cell-attached patch-clamp electrophysiology and pressure-clamp stimulation to functionally examine large numbers of membrane patches from cells expressing Piezo1 endogenously at low levels and cells overexpressing Piezo1 at high levels. Our data, together with stochastic simulations of Piezo1 spatial distributions, show that both at endogenous densities (1–2 channels/μm2), and at non-physiological densities (10–100 channels/μm2) predicted to cause substantial footprint overlap, Piezo1 density has no effect on its pressure sensitivity or open probability in the nominal absence of membrane tension. The results suggest that Piezo channels, at densities likely to be physiologically relevant, inherently behave as independent mechanotransducers. We propose that this property is essential for cells to transduce forces homogeneously across the entire cell membrane.https://elifesciences.org/articles/70988mechanotransductionPiezo1force-gated ion channelclusteringcooperativity
spellingShingle Amanda H Lewis
Jörg Grandl
Piezo1 ion channels inherently function as independent mechanotransducers
eLife
mechanotransduction
Piezo1
force-gated ion channel
clustering
cooperativity
title Piezo1 ion channels inherently function as independent mechanotransducers
title_full Piezo1 ion channels inherently function as independent mechanotransducers
title_fullStr Piezo1 ion channels inherently function as independent mechanotransducers
title_full_unstemmed Piezo1 ion channels inherently function as independent mechanotransducers
title_short Piezo1 ion channels inherently function as independent mechanotransducers
title_sort piezo1 ion channels inherently function as independent mechanotransducers
topic mechanotransduction
Piezo1
force-gated ion channel
clustering
cooperativity
url https://elifesciences.org/articles/70988
work_keys_str_mv AT amandahlewis piezo1ionchannelsinherentlyfunctionasindependentmechanotransducers
AT jorggrandl piezo1ionchannelsinherentlyfunctionasindependentmechanotransducers