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Selective activation of mechanosensitive ion channels using magnetic particles

This study reports the preliminary development of a novel magnetic particle-based technique that permits the application of highly localized mechanical forces directly to specific regions of an ion-channel structure. We demonstrate that this approach can be used to directly and selectively activate...

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Detalles Bibliográficos
Autores principales: Hughes, Steven, McBain, Stuart, Dobson, Jon, El Haj, Alicia J
Formato: Texto
Lenguaje:English
Publicado: The Royal Society 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2495030/
https://www.ncbi.nlm.nih.gov/pubmed/18077244
http://dx.doi.org/10.1098/rsif.2007.1274
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author Hughes, Steven
McBain, Stuart
Dobson, Jon
El Haj, Alicia J
author_facet Hughes, Steven
McBain, Stuart
Dobson, Jon
El Haj, Alicia J
author_sort Hughes, Steven
collection PubMed
description This study reports the preliminary development of a novel magnetic particle-based technique that permits the application of highly localized mechanical forces directly to specific regions of an ion-channel structure. We demonstrate that this approach can be used to directly and selectively activate a mechanosensitive ion channel of interest, namely TREK-1. It is shown that manipulation of particles targeted against the extended extracellular loop region of TREK-1 leads to changes in whole-cell currents consistent with changes in TREK-1 activity. Responses were absent when particles were coated with RGD (Arg–Gly–Asp) peptide or when magnetic fields were applied in the absence of magnetic particles. It is concluded that changes in whole-cell current are the result of direct force application to the extracellular loop region of TREK-1 and thus these results implicate this region of the channel structure in mechano-gating. It is hypothesized that the extended loop region of TREK-1 may act as a tension spring that acts to regulate sensitivity to mechanical forces, in a nature similar to that described for MscL. The development of a technique that permits the direct manipulation of mechanosensitive ion channels in real time without the need for pharmacological drugs has huge potential benefits not only for basic biological research of ion-channel gating mechanisms, but also potentially as a tool for the treatment of human diseases caused by ion-channel dysfunction.
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spelling pubmed-24950302008-12-29 Selective activation of mechanosensitive ion channels using magnetic particles Hughes, Steven McBain, Stuart Dobson, Jon El Haj, Alicia J J R Soc Interface Research Article This study reports the preliminary development of a novel magnetic particle-based technique that permits the application of highly localized mechanical forces directly to specific regions of an ion-channel structure. We demonstrate that this approach can be used to directly and selectively activate a mechanosensitive ion channel of interest, namely TREK-1. It is shown that manipulation of particles targeted against the extended extracellular loop region of TREK-1 leads to changes in whole-cell currents consistent with changes in TREK-1 activity. Responses were absent when particles were coated with RGD (Arg–Gly–Asp) peptide or when magnetic fields were applied in the absence of magnetic particles. It is concluded that changes in whole-cell current are the result of direct force application to the extracellular loop region of TREK-1 and thus these results implicate this region of the channel structure in mechano-gating. It is hypothesized that the extended loop region of TREK-1 may act as a tension spring that acts to regulate sensitivity to mechanical forces, in a nature similar to that described for MscL. The development of a technique that permits the direct manipulation of mechanosensitive ion channels in real time without the need for pharmacological drugs has huge potential benefits not only for basic biological research of ion-channel gating mechanisms, but also potentially as a tool for the treatment of human diseases caused by ion-channel dysfunction. The Royal Society 2007-12-11 2008-08-06 /pmc/articles/PMC2495030/ /pubmed/18077244 http://dx.doi.org/10.1098/rsif.2007.1274 Text en Copyright © 2007 The Royal Society http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hughes, Steven
McBain, Stuart
Dobson, Jon
El Haj, Alicia J
Selective activation of mechanosensitive ion channels using magnetic particles
title Selective activation of mechanosensitive ion channels using magnetic particles
title_full Selective activation of mechanosensitive ion channels using magnetic particles
title_fullStr Selective activation of mechanosensitive ion channels using magnetic particles
title_full_unstemmed Selective activation of mechanosensitive ion channels using magnetic particles
title_short Selective activation of mechanosensitive ion channels using magnetic particles
title_sort selective activation of mechanosensitive ion channels using magnetic particles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2495030/
https://www.ncbi.nlm.nih.gov/pubmed/18077244
http://dx.doi.org/10.1098/rsif.2007.1274
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