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BK channel inhibition by strong extracellular acidification
Mammalian BK-type voltage- and Ca(2+)-dependent K(+) channels are found in a wide range of cells and intracellular organelles. Among different loci, the composition of the extracellular microenvironment, including pH, may differ substantially. For example, it has been reported that BK channels are e...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054526/ https://www.ncbi.nlm.nih.gov/pubmed/29963986 http://dx.doi.org/10.7554/eLife.38060 |
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author | Zhou, Yu Xia, Xiao-Ming Lingle, Christopher J |
author_facet | Zhou, Yu Xia, Xiao-Ming Lingle, Christopher J |
author_sort | Zhou, Yu |
collection | PubMed |
description | Mammalian BK-type voltage- and Ca(2+)-dependent K(+) channels are found in a wide range of cells and intracellular organelles. Among different loci, the composition of the extracellular microenvironment, including pH, may differ substantially. For example, it has been reported that BK channels are expressed in lysosomes with their extracellular side facing the strongly acidified lysosomal lumen (pH ~4.5). Here we show that BK activation is strongly and reversibly inhibited by extracellular H(+), with its conductance-voltage relationship shifted by more than +100 mV at pH(O) 4. Our results reveal that this inhibition is mainly caused by H(+) inhibition of BK voltage-sensor (VSD) activation through three acidic residues on the extracellular side of BK VSD. Given that these key residues (D133, D147, D153) are highly conserved among members in the voltage-dependent cation channel superfamily, the mechanism underlying BK inhibition by extracellular acidification might also be applicable to other members in the family. |
format | Online Article Text |
id | pubmed-6054526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-60545262018-07-23 BK channel inhibition by strong extracellular acidification Zhou, Yu Xia, Xiao-Ming Lingle, Christopher J eLife Structural Biology and Molecular Biophysics Mammalian BK-type voltage- and Ca(2+)-dependent K(+) channels are found in a wide range of cells and intracellular organelles. Among different loci, the composition of the extracellular microenvironment, including pH, may differ substantially. For example, it has been reported that BK channels are expressed in lysosomes with their extracellular side facing the strongly acidified lysosomal lumen (pH ~4.5). Here we show that BK activation is strongly and reversibly inhibited by extracellular H(+), with its conductance-voltage relationship shifted by more than +100 mV at pH(O) 4. Our results reveal that this inhibition is mainly caused by H(+) inhibition of BK voltage-sensor (VSD) activation through three acidic residues on the extracellular side of BK VSD. Given that these key residues (D133, D147, D153) are highly conserved among members in the voltage-dependent cation channel superfamily, the mechanism underlying BK inhibition by extracellular acidification might also be applicable to other members in the family. eLife Sciences Publications, Ltd 2018-07-02 /pmc/articles/PMC6054526/ /pubmed/29963986 http://dx.doi.org/10.7554/eLife.38060 Text en © 2018, Zhou et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Structural Biology and Molecular Biophysics Zhou, Yu Xia, Xiao-Ming Lingle, Christopher J BK channel inhibition by strong extracellular acidification |
title | BK channel inhibition by strong extracellular acidification |
title_full | BK channel inhibition by strong extracellular acidification |
title_fullStr | BK channel inhibition by strong extracellular acidification |
title_full_unstemmed | BK channel inhibition by strong extracellular acidification |
title_short | BK channel inhibition by strong extracellular acidification |
title_sort | bk channel inhibition by strong extracellular acidification |
topic | Structural Biology and Molecular Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054526/ https://www.ncbi.nlm.nih.gov/pubmed/29963986 http://dx.doi.org/10.7554/eLife.38060 |
work_keys_str_mv | AT zhouyu bkchannelinhibitionbystrongextracellularacidification AT xiaxiaoming bkchannelinhibitionbystrongextracellularacidification AT linglechristopherj bkchannelinhibitionbystrongextracellularacidification |