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Mechanically-gated Ion Channels

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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...

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Updated: Sep 12, 2025

One-channel Cell-attached Patch-clamp Recording

One-channel Cell-attached Patch-clamp Recording

Published on: June 9, 2014

Oxidative modulation of Piezo1 channels.

N Novosolova¹, N Braidotti², T Patinen¹

¹A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, 70210, Finland.

|August 8, 2025

Summary

Oxidative stress inhibits Piezo1 channel activity by oxidizing key amino acids, impacting cellular mechanics in diseases. This redox regulation of Piezo1 channels is crucial in conditions involving oxidative stress.

Keywords:

Hydrogen peroxide Mechanoreceptors Oxidation Oxidative stress Piezo1 channel

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Area of Science:

Cell biology
Biophysics
Neuroscience

Background:

Mechanosensitive Piezo1 channels are implicated in various disease pathologies.
Oxidative stress, characterized by reactive oxygen species (ROS), is common in neurodegenerative diseases.
The redox regulation of Piezo1 channel function remains largely unexplored.

Purpose of the Study:

To investigate the effect of oxidative stress on Piezo1 channel activity and calcium permeability.
To determine if Piezo1 channel activation influences endogenous reactive oxygen species (ROS) generation.
To elucidate the specific amino acid residues involved in the redox modulation of Piezo1.

Main Methods:

Utilized red blood cells (RBCs) and HEK293T cells expressing Piezo1.
Employed flow cytometry, Ca2+ imaging, patch clamp, and microaspiration techniques.
Used selective oxidants (H2O2, Chloramine-T, DTNB) and antioxidants (N-acetylcysteine, dithiothreitol), and the H2O2 sensor HyPer7.

Main Results:

Cell-permeable oxidants (H2O2, Chloramine-T) and membrane-impermeable DTNB inhibited Yoda1-induced Piezo1 activation.
Hydrogen peroxide reduced the mechanical sensitivity of Piezo1 in RBCs.
Antioxidants reversed the inhibitory effects, and Nrf2 overexpression did not prevent inhibition, suggesting a membrane-delimited site of action, with methionines playing a predominant role.

Conclusions:

Oxidative stress, through the oxidation of cysteines and methionines, inhibits Piezo1 channel activity.
Piezo1 activation can slightly increase endogenous H2O2 production.
Redox modulation of Piezo1 channels is a significant factor in disease pathology under oxidative stress conditions.