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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ilyaskin, Alexandr V., Diakov, Alexei, Korbmacher, Christoph, Haerteis, Silke
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