Cargando…
Bile acids potentiate proton‐activated currents in Xenopus laevis oocytes expressing human acid‐sensing ion channel (ASIC1a)
Acid‐sensing ion channels (ASICs) are nonvoltage‐gated sodium channels transiently activated by extracellular protons and belong to the epithelial sodium channel (ENaC)/Degenerin (DEG) family of ion channels. Bile acids have been shown to activate two members of this family, the bile acid‐sensitive...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309578/ https://www.ncbi.nlm.nih.gov/pubmed/28193786 http://dx.doi.org/10.14814/phy2.13132 |
_version_ | 1782507730382094336 |
---|---|
author | Ilyaskin, Alexandr V. Diakov, Alexei Korbmacher, Christoph Haerteis, Silke |
author_facet | Ilyaskin, Alexandr V. Diakov, Alexei Korbmacher, Christoph Haerteis, Silke |
author_sort | Ilyaskin, Alexandr V. |
collection | PubMed |
description | Acid‐sensing ion channels (ASICs) are nonvoltage‐gated sodium channels transiently activated by extracellular protons and belong to the epithelial sodium channel (ENaC)/Degenerin (DEG) family of ion channels. Bile acids have been shown to activate two members of this family, the bile acid‐sensitive ion channel (BASIC) and ENaC. To investigate whether bile acids also modulate ASIC function, human ASIC1a was heterologously expressed in Xenopus laevis oocytes. Exposing oocytes to tauro‐conjugated cholic (t‐CA), deoxycholic (t‐DCA), and chenodeoxycholic (t‐CDCA) acid at pH 7.4 did not activate ASIC1a‐mediated whole‐cell currents. However, in ASIC1a expressing oocytes the whole‐cell currents elicited by pH 5.5 were significantly increased in the presence of these bile acids. Single‐channel recordings in outside‐out patches confirmed that t‐DCA enhanced the stimulatory effect of pH 5.5 on ASIC1a channel activity. Interestingly, t‐DCA reduced single‐channel current amplitude by ~15% which suggests an interaction of t‐DCA with a region close to the channel pore. Molecular docking predicted binding of bile acids to the pore region near the degenerin site (G433) in the open conformation of the channel. Site‐directed mutagenesis demonstrated that the amino acid residue G433 is critically involved in the potentiating effect of bile acids on ASIC1a activation by protons. |
format | Online Article Text |
id | pubmed-5309578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53095782017-02-22 Bile acids potentiate proton‐activated currents in Xenopus laevis oocytes expressing human acid‐sensing ion channel (ASIC1a) Ilyaskin, Alexandr V. Diakov, Alexei Korbmacher, Christoph Haerteis, Silke Physiol Rep Original Research Acid‐sensing ion channels (ASICs) are nonvoltage‐gated sodium channels transiently activated by extracellular protons and belong to the epithelial sodium channel (ENaC)/Degenerin (DEG) family of ion channels. Bile acids have been shown to activate two members of this family, the bile acid‐sensitive ion channel (BASIC) and ENaC. To investigate whether bile acids also modulate ASIC function, human ASIC1a was heterologously expressed in Xenopus laevis oocytes. Exposing oocytes to tauro‐conjugated cholic (t‐CA), deoxycholic (t‐DCA), and chenodeoxycholic (t‐CDCA) acid at pH 7.4 did not activate ASIC1a‐mediated whole‐cell currents. However, in ASIC1a expressing oocytes the whole‐cell currents elicited by pH 5.5 were significantly increased in the presence of these bile acids. Single‐channel recordings in outside‐out patches confirmed that t‐DCA enhanced the stimulatory effect of pH 5.5 on ASIC1a channel activity. Interestingly, t‐DCA reduced single‐channel current amplitude by ~15% which suggests an interaction of t‐DCA with a region close to the channel pore. Molecular docking predicted binding of bile acids to the pore region near the degenerin site (G433) in the open conformation of the channel. Site‐directed mutagenesis demonstrated that the amino acid residue G433 is critically involved in the potentiating effect of bile acids on ASIC1a activation by protons. John Wiley and Sons Inc. 2017-02-13 /pmc/articles/PMC5309578/ /pubmed/28193786 http://dx.doi.org/10.14814/phy2.13132 Text en © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Ilyaskin, Alexandr V. Diakov, Alexei Korbmacher, Christoph Haerteis, Silke Bile acids potentiate proton‐activated currents in Xenopus laevis oocytes expressing human acid‐sensing ion channel (ASIC1a) |
title | Bile acids potentiate proton‐activated currents in Xenopus laevis oocytes expressing human acid‐sensing ion channel (ASIC1a) |
title_full | Bile acids potentiate proton‐activated currents in Xenopus laevis oocytes expressing human acid‐sensing ion channel (ASIC1a) |
title_fullStr | Bile acids potentiate proton‐activated currents in Xenopus laevis oocytes expressing human acid‐sensing ion channel (ASIC1a) |
title_full_unstemmed | Bile acids potentiate proton‐activated currents in Xenopus laevis oocytes expressing human acid‐sensing ion channel (ASIC1a) |
title_short | Bile acids potentiate proton‐activated currents in Xenopus laevis oocytes expressing human acid‐sensing ion channel (ASIC1a) |
title_sort | bile acids potentiate proton‐activated currents in xenopus laevis oocytes expressing human acid‐sensing ion channel (asic1a) |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309578/ https://www.ncbi.nlm.nih.gov/pubmed/28193786 http://dx.doi.org/10.14814/phy2.13132 |
work_keys_str_mv | AT ilyaskinalexandrv bileacidspotentiateprotonactivatedcurrentsinxenopuslaevisoocytesexpressinghumanacidsensingionchannelasic1a AT diakovalexei bileacidspotentiateprotonactivatedcurrentsinxenopuslaevisoocytesexpressinghumanacidsensingionchannelasic1a AT korbmacherchristoph bileacidspotentiateprotonactivatedcurrentsinxenopuslaevisoocytesexpressinghumanacidsensingionchannelasic1a AT haerteissilke bileacidspotentiateprotonactivatedcurrentsinxenopuslaevisoocytesexpressinghumanacidsensingionchannelasic1a |