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Properties of the Inner Pore Region of TRPV1 Channels Revealed by Block with Quaternary Ammoniums

The transient receptor potential vanilloid 1 (TRPV1) nonselective cationic channel is a polymodal receptor that activates in response to a wide variety of stimuli. To date, little structural information about this channel is available. Here, we used quaternary ammonium ions (QAs) of different sizes...

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Autores principales: Jara-Oseguera, Andrés, Llorente, Itzel, Rosenbaum, Tamara, Islas, León D.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571972/
https://www.ncbi.nlm.nih.gov/pubmed/18955595
http://dx.doi.org/10.1085/jgp.200810051
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author Jara-Oseguera, Andrés
Llorente, Itzel
Rosenbaum, Tamara
Islas, León D.
author_facet Jara-Oseguera, Andrés
Llorente, Itzel
Rosenbaum, Tamara
Islas, León D.
author_sort Jara-Oseguera, Andrés
collection PubMed
description The transient receptor potential vanilloid 1 (TRPV1) nonselective cationic channel is a polymodal receptor that activates in response to a wide variety of stimuli. To date, little structural information about this channel is available. Here, we used quaternary ammonium ions (QAs) of different sizes in an effort to gain some insight into the nature and dimensions of the pore of TRPV1. We found that all four QAs used, tetraethylammonium (TEA), tetrapropylammonium (TPrA), tetrabutylammonium, and tetrapentylammonium, block the TRPV1 channel from the intracellular face of the channel in a voltage-dependent manner, and that block by these molecules occurs with different kinetics, with the bigger molecules becoming slower blockers. We also found that TPrA and the larger QAs can only block the channel in the open state, and that they interfere with the channel's activation gate upon closing, which is observed as a slowing of tail current kinetics. TEA does not interfere with the activation gate, indicating that this molecule can reside in its blocking site even when the channel is closed. The dependence of the rate constants on the size of the blocker suggests a size of around 10 Å for the inner pore of TRPV1 channels.
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spelling pubmed-25719722009-05-01 Properties of the Inner Pore Region of TRPV1 Channels Revealed by Block with Quaternary Ammoniums Jara-Oseguera, Andrés Llorente, Itzel Rosenbaum, Tamara Islas, León D. J Gen Physiol Articles The transient receptor potential vanilloid 1 (TRPV1) nonselective cationic channel is a polymodal receptor that activates in response to a wide variety of stimuli. To date, little structural information about this channel is available. Here, we used quaternary ammonium ions (QAs) of different sizes in an effort to gain some insight into the nature and dimensions of the pore of TRPV1. We found that all four QAs used, tetraethylammonium (TEA), tetrapropylammonium (TPrA), tetrabutylammonium, and tetrapentylammonium, block the TRPV1 channel from the intracellular face of the channel in a voltage-dependent manner, and that block by these molecules occurs with different kinetics, with the bigger molecules becoming slower blockers. We also found that TPrA and the larger QAs can only block the channel in the open state, and that they interfere with the channel's activation gate upon closing, which is observed as a slowing of tail current kinetics. TEA does not interfere with the activation gate, indicating that this molecule can reside in its blocking site even when the channel is closed. The dependence of the rate constants on the size of the blocker suggests a size of around 10 Å for the inner pore of TRPV1 channels. The Rockefeller University Press 2008-11 /pmc/articles/PMC2571972/ /pubmed/18955595 http://dx.doi.org/10.1085/jgp.200810051 Text en © 2008 Jara-Oseguera et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Articles
Jara-Oseguera, Andrés
Llorente, Itzel
Rosenbaum, Tamara
Islas, León D.
Properties of the Inner Pore Region of TRPV1 Channels Revealed by Block with Quaternary Ammoniums
title Properties of the Inner Pore Region of TRPV1 Channels Revealed by Block with Quaternary Ammoniums
title_full Properties of the Inner Pore Region of TRPV1 Channels Revealed by Block with Quaternary Ammoniums
title_fullStr Properties of the Inner Pore Region of TRPV1 Channels Revealed by Block with Quaternary Ammoniums
title_full_unstemmed Properties of the Inner Pore Region of TRPV1 Channels Revealed by Block with Quaternary Ammoniums
title_short Properties of the Inner Pore Region of TRPV1 Channels Revealed by Block with Quaternary Ammoniums
title_sort properties of the inner pore region of trpv1 channels revealed by block with quaternary ammoniums
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571972/
https://www.ncbi.nlm.nih.gov/pubmed/18955595
http://dx.doi.org/10.1085/jgp.200810051
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