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Proton block of proton-activated TRPV1 current
The TRPV1 cation channel is a polymodal nociceptor that is activated by heat and ligands such as capsaicin and is highly sensitive to changes in extracellular pH. In the body core, where temperature is usually stable and capsaicin is normally absent, H(+) released in response to ischemia, tissue inj...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516785/ https://www.ncbi.nlm.nih.gov/pubmed/26170176 http://dx.doi.org/10.1085/jgp.201511386 |
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author | Lee, Bo Hyun Zheng, Jie |
author_facet | Lee, Bo Hyun Zheng, Jie |
author_sort | Lee, Bo Hyun |
collection | PubMed |
description | The TRPV1 cation channel is a polymodal nociceptor that is activated by heat and ligands such as capsaicin and is highly sensitive to changes in extracellular pH. In the body core, where temperature is usually stable and capsaicin is normally absent, H(+) released in response to ischemia, tissue injury, or inflammation is the best-known endogenous TRPV1 agonist, activating the channel to mediate pain and vasodilation. Paradoxically, removal of H(+) elicits a transient increase in TRPV1 current that is much larger than the initial H(+)-activated current. We found that this prominent OFF response is caused by rapid recovery from H(+) inhibition of the excitatory current carried by H(+)-activated TRPV1 channels. H(+) inhibited current by interfering with ion permeation. The degree of inhibition is voltage and permeant ion dependent, and it can be affected but not eliminated by mutations to acidic residues within or near the ion selectivity filter. The opposing H(+)-mediated gating and permeation effects produce complex current responses under different cellular conditions that are expected to greatly affect the response of nociceptive neurons and other TRPV1-expressing cells. |
format | Online Article Text |
id | pubmed-4516785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-45167852016-01-31 Proton block of proton-activated TRPV1 current Lee, Bo Hyun Zheng, Jie J Gen Physiol Research Articles The TRPV1 cation channel is a polymodal nociceptor that is activated by heat and ligands such as capsaicin and is highly sensitive to changes in extracellular pH. In the body core, where temperature is usually stable and capsaicin is normally absent, H(+) released in response to ischemia, tissue injury, or inflammation is the best-known endogenous TRPV1 agonist, activating the channel to mediate pain and vasodilation. Paradoxically, removal of H(+) elicits a transient increase in TRPV1 current that is much larger than the initial H(+)-activated current. We found that this prominent OFF response is caused by rapid recovery from H(+) inhibition of the excitatory current carried by H(+)-activated TRPV1 channels. H(+) inhibited current by interfering with ion permeation. The degree of inhibition is voltage and permeant ion dependent, and it can be affected but not eliminated by mutations to acidic residues within or near the ion selectivity filter. The opposing H(+)-mediated gating and permeation effects produce complex current responses under different cellular conditions that are expected to greatly affect the response of nociceptive neurons and other TRPV1-expressing cells. The Rockefeller University Press 2015-08 /pmc/articles/PMC4516785/ /pubmed/26170176 http://dx.doi.org/10.1085/jgp.201511386 Text en © 2015 Lee and Zheng 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.rupress.org/terms). 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 | Research Articles Lee, Bo Hyun Zheng, Jie Proton block of proton-activated TRPV1 current |
title | Proton block of proton-activated TRPV1 current |
title_full | Proton block of proton-activated TRPV1 current |
title_fullStr | Proton block of proton-activated TRPV1 current |
title_full_unstemmed | Proton block of proton-activated TRPV1 current |
title_short | Proton block of proton-activated TRPV1 current |
title_sort | proton block of proton-activated trpv1 current |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516785/ https://www.ncbi.nlm.nih.gov/pubmed/26170176 http://dx.doi.org/10.1085/jgp.201511386 |
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