1. Physics of Living Systems
  2. Neuroscience
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Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension

  1. Amanda H Lewis
  2. Jorg Grandl  Is a corresponding author
  1. Duke University Medical Center, United States
Research Article
  • Cited 82
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Cite this article as: eLife 2015;4:e12088 doi: 10.7554/eLife.12088

Abstract

Piezo1 ion channels mediate the conversion of mechanical forces into electrical signals and are critical for responsiveness to touch in metazoans. The apparent mechanical sensitivity of Piezo1 varies substantially across cellular environments, stimulating methods and protocols, raising the fundamental questions of what precise physical stimulus activates the channel and how its stimulus sensitivity is regulated. Here, we measured Piezo1 currents evoked by membrane stretch in three patch configurations, while simultaneously visualizing and measuring membrane geometry. Building on this approach, we developed protocols to minimize resting membrane curvature and tension prior to probing Piezo activity. We find that Piezo1 responds to lateral membrane tension with exquisite sensitivity as compared to other mechanically activated channels and that resting tension can drive channel inactivation, thereby tuning overall mechanical sensitivity of Piezo1. Our results explain how Piezo1 can function efficiently and with adaptable sensitivity as a sensor of mechanical stimulation in diverse cellular contexts.

Article and author information

Author details

  1. Amanda H Lewis

    Department of Neurobiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jorg Grandl

    Department of Neurobiology, Duke University Medical Center, Durham, United States
    For correspondence
    grandl@neuro.duke.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Richard Aldrich, The University of Texas at Austin, United States

Publication history

  1. Received: October 5, 2015
  2. Accepted: November 26, 2015
  3. Accepted Manuscript published: December 8, 2015 (version 1)
  4. Version of Record published: December 30, 2015 (version 2)

Copyright

© 2015, Lewis & Grandl

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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