Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis

Abstract The archetypal TRPM2-like channel of the sea anemone Nematostella vectensis is gated by ADPR like its human orthologue but additionally exhibits properties of other vertebrate TRPM channels. Thus it can help towards an understanding of gating and regulation of the whole subfamily. To elucid...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Frank J. P. Kühn, Winking Mathis, Kühn Cornelia, Daniel C. Hoffmann, Andreas Lückhoff
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a0f9940f18d43808c48d95e6093661a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0a0f9940f18d43808c48d95e6093661a
record_format	dspace
spelling	oai:doaj.org-article:0a0f9940f18d43808c48d95e6093661a2021-12-02T11:41:21ZModulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis10.1038/s41598-017-07652-42045-2322https://doaj.org/article/0a0f9940f18d43808c48d95e6093661a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07652-4https://doaj.org/toc/2045-2322Abstract The archetypal TRPM2-like channel of the sea anemone Nematostella vectensis is gated by ADPR like its human orthologue but additionally exhibits properties of other vertebrate TRPM channels. Thus it can help towards an understanding of gating and regulation of the whole subfamily. To elucidate further the role of Ca2+ as a co-factor of ADPR, we exploited 2-aminoethyl diphenylborinate (2-APB), previously shown to exert either inhibitory or stimulatory effects on diverse TRPM channels, or both in a concentration-dependent manner. 2-APB in high concentrations (1 mM) induced large, non-inactivating currents through nvTRPM2. In lower concentrations (≤0.5 mM), it prevented the fast current inactivation typical for nvTRPM2 stimulated with ADPR. Both these effects were rapidly reversed after wash-out of 2-APB, in contrast to a considerable lag time of their onset. A detailed analysis of nvTRPM2 mutants with modified selectivity filter or reduced ADP-ribose sensitivity revealed that the actions of 2-APB depend on its access to the pore which is enhanced by channel opening. Moreover, access of Ca2+ to the pore is decisive which again depends on the open state of the channel. We conclude that separate regulatory processes by Ca2+ on the pore can be discriminated with the aid of 2-APB.Frank J. P. KühnWinking MathisKühn CorneliaDaniel C. HoffmannAndreas LückhoffNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Frank J. P. Kühn Winking Mathis Kühn Cornelia Daniel C. Hoffmann Andreas Lückhoff Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis
description	Abstract The archetypal TRPM2-like channel of the sea anemone Nematostella vectensis is gated by ADPR like its human orthologue but additionally exhibits properties of other vertebrate TRPM channels. Thus it can help towards an understanding of gating and regulation of the whole subfamily. To elucidate further the role of Ca2+ as a co-factor of ADPR, we exploited 2-aminoethyl diphenylborinate (2-APB), previously shown to exert either inhibitory or stimulatory effects on diverse TRPM channels, or both in a concentration-dependent manner. 2-APB in high concentrations (1 mM) induced large, non-inactivating currents through nvTRPM2. In lower concentrations (≤0.5 mM), it prevented the fast current inactivation typical for nvTRPM2 stimulated with ADPR. Both these effects were rapidly reversed after wash-out of 2-APB, in contrast to a considerable lag time of their onset. A detailed analysis of nvTRPM2 mutants with modified selectivity filter or reduced ADP-ribose sensitivity revealed that the actions of 2-APB depend on its access to the pore which is enhanced by channel opening. Moreover, access of Ca2+ to the pore is decisive which again depends on the open state of the channel. We conclude that separate regulatory processes by Ca2+ on the pore can be discriminated with the aid of 2-APB.
format	article
author	Frank J. P. Kühn Winking Mathis Kühn Cornelia Daniel C. Hoffmann Andreas Lückhoff
author_facet	Frank J. P. Kühn Winking Mathis Kühn Cornelia Daniel C. Hoffmann Andreas Lückhoff
author_sort	Frank J. P. Kühn
title	Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis
title_short	Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis
title_full	Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis
title_fullStr	Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis
title_full_unstemmed	Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis
title_sort	modulation of activation and inactivation by ca2+ and 2-apb in the pore of an archetypal trpm channel from nematostella vectensis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0a0f9940f18d43808c48d95e6093661a
work_keys_str_mv	AT frankjpkuhn modulationofactivationandinactivationbyca2and2apbintheporeofanarchetypaltrpmchannelfromnematostellavectensis AT winkingmathis modulationofactivationandinactivationbyca2and2apbintheporeofanarchetypaltrpmchannelfromnematostellavectensis AT kuhncornelia modulationofactivationandinactivationbyca2and2apbintheporeofanarchetypaltrpmchannelfromnematostellavectensis AT danielchoffmann modulationofactivationandinactivationbyca2and2apbintheporeofanarchetypaltrpmchannelfromnematostellavectensis AT andreasluckhoff modulationofactivationandinactivationbyca2and2apbintheporeofanarchetypaltrpmchannelfromnematostellavectensis
_version_	1718395383481106432

Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis

Ejemplares similares