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Selective Chemical Activation of Piezo1 in Leukemia Cell Membrane: Single Channel Analysis

Piezo1/2 are mechanosensitive calcium-permeable channels that can be activated by various modes of membrane deformation. The identification of the small molecule Yoda1, a synthetic Piezo1 agonist, revealed the possibility of chemical activation of the channel. Stimulating effects of Yoda1 on Piezo1...

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Autores principales: Vasileva, Valeria, Morachevskaya, Elena, Sudarikova, Anastasia, Negulyaev, Yuri, Chubinskiy-Nadezhdin, Vladislav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346046/
https://www.ncbi.nlm.nih.gov/pubmed/34360605
http://dx.doi.org/10.3390/ijms22157839
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author Vasileva, Valeria
Morachevskaya, Elena
Sudarikova, Anastasia
Negulyaev, Yuri
Chubinskiy-Nadezhdin, Vladislav
author_facet Vasileva, Valeria
Morachevskaya, Elena
Sudarikova, Anastasia
Negulyaev, Yuri
Chubinskiy-Nadezhdin, Vladislav
author_sort Vasileva, Valeria
collection PubMed
description Piezo1/2 are mechanosensitive calcium-permeable channels that can be activated by various modes of membrane deformation. The identification of the small molecule Yoda1, a synthetic Piezo1 agonist, revealed the possibility of chemical activation of the channel. Stimulating effects of Yoda1 on Piezo1 have been mainly documented using over-expressing cellular systems or channel proteins incorporated in artificial lipid bilayers. However, the activating effect of Yoda1 on native Piezo1 channels in the plasma membrane of living cells remains generally undefined, despite the increasing number of studies in which the agonist is utilized as a functional tool to reveal the contribution of Piezo1 to cellular reactions. In the current study, we used the human myeloid leukemia K562 cell line as a suitable model to examine chemically induced Piezo1 activity with the use of the patch-clamp technique in various specific modes. The functional expression of Piezo1 in leukemia cells was evidenced using a combinative approach, including single channel patch-clamp measurements. Utilizing our established single-current whole-cell assay on K562 cells, we have shown, for the first time, the selective real-time chemical activation of endogenously expressed Piezo1. Extracellular application of 0.5–1 µM Yoda1 effectively stimulated single Piezo1 currents in the cell membrane.
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spelling pubmed-83460462021-08-07 Selective Chemical Activation of Piezo1 in Leukemia Cell Membrane: Single Channel Analysis Vasileva, Valeria Morachevskaya, Elena Sudarikova, Anastasia Negulyaev, Yuri Chubinskiy-Nadezhdin, Vladislav Int J Mol Sci Brief Report Piezo1/2 are mechanosensitive calcium-permeable channels that can be activated by various modes of membrane deformation. The identification of the small molecule Yoda1, a synthetic Piezo1 agonist, revealed the possibility of chemical activation of the channel. Stimulating effects of Yoda1 on Piezo1 have been mainly documented using over-expressing cellular systems or channel proteins incorporated in artificial lipid bilayers. However, the activating effect of Yoda1 on native Piezo1 channels in the plasma membrane of living cells remains generally undefined, despite the increasing number of studies in which the agonist is utilized as a functional tool to reveal the contribution of Piezo1 to cellular reactions. In the current study, we used the human myeloid leukemia K562 cell line as a suitable model to examine chemically induced Piezo1 activity with the use of the patch-clamp technique in various specific modes. The functional expression of Piezo1 in leukemia cells was evidenced using a combinative approach, including single channel patch-clamp measurements. Utilizing our established single-current whole-cell assay on K562 cells, we have shown, for the first time, the selective real-time chemical activation of endogenously expressed Piezo1. Extracellular application of 0.5–1 µM Yoda1 effectively stimulated single Piezo1 currents in the cell membrane. MDPI 2021-07-22 /pmc/articles/PMC8346046/ /pubmed/34360605 http://dx.doi.org/10.3390/ijms22157839 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Vasileva, Valeria
Morachevskaya, Elena
Sudarikova, Anastasia
Negulyaev, Yuri
Chubinskiy-Nadezhdin, Vladislav
Selective Chemical Activation of Piezo1 in Leukemia Cell Membrane: Single Channel Analysis
title Selective Chemical Activation of Piezo1 in Leukemia Cell Membrane: Single Channel Analysis
title_full Selective Chemical Activation of Piezo1 in Leukemia Cell Membrane: Single Channel Analysis
title_fullStr Selective Chemical Activation of Piezo1 in Leukemia Cell Membrane: Single Channel Analysis
title_full_unstemmed Selective Chemical Activation of Piezo1 in Leukemia Cell Membrane: Single Channel Analysis
title_short Selective Chemical Activation of Piezo1 in Leukemia Cell Membrane: Single Channel Analysis
title_sort selective chemical activation of piezo1 in leukemia cell membrane: single channel analysis
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346046/
https://www.ncbi.nlm.nih.gov/pubmed/34360605
http://dx.doi.org/10.3390/ijms22157839
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