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Heterodimerization of two pore domain K(+) channel TASK1 and TALK2 in living heterologous expression systems

Two-pore-domain K(+) (K(2P)) channels sense a wide variety of stimuli such as mechanical stress, inhalational anesthetics, and changes in extracellular pH or temperature. The K(2P) channel activity forms a background K(+) current and, thereby, contributes to resting membrane potentials. Six subfamil...

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Detalles Bibliográficos
Autores principales: Suzuki, Yoshiaki, Tsutsumi, Kanako, Miyamoto, Tatsuya, Yamamura, Hisao, Imaizumi, Yuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634629/
https://www.ncbi.nlm.nih.gov/pubmed/29016681
http://dx.doi.org/10.1371/journal.pone.0186252
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author Suzuki, Yoshiaki
Tsutsumi, Kanako
Miyamoto, Tatsuya
Yamamura, Hisao
Imaizumi, Yuji
author_facet Suzuki, Yoshiaki
Tsutsumi, Kanako
Miyamoto, Tatsuya
Yamamura, Hisao
Imaizumi, Yuji
author_sort Suzuki, Yoshiaki
collection PubMed
description Two-pore-domain K(+) (K(2P)) channels sense a wide variety of stimuli such as mechanical stress, inhalational anesthetics, and changes in extracellular pH or temperature. The K(2P) channel activity forms a background K(+) current and, thereby, contributes to resting membrane potentials. Six subfamilies including fifteen subtypes of K(2P) channels have been identified. Each K(2P) channel molecule with two pores consists of a homodimer of each subtype. In addition, a few heterodimers mainly within the same subfamilies have been found recently. In the present study, the possibility of heterodimerization between TASK1 (TWIK-Related Acid-Sensitive K(+) channel) and TALK2 (TWIK-Related Alkaline pH-Activated K(+) channel) was examined. These channels belong to separate subfamilies and show extremely different channel properties. Surprisingly, single molecular imaging analyses in this study using a total internal reflection microscope suggested the heterodimerization of TASK1 and TALK2 in a pancreatic cell line, QGP-1. This heterodimer was also detected using a bimolecular fluorescence complementation assay in a HEK293 heterologous expression system. Fluorescence resonance energy transfer analyses showed that the affinity between TASK1 and TALK2 appeared to be close to those of homodimers. Whole-cell patch-clamp recordings revealed that TASK1 currents in HEK293 cells were significantly attenuated by co-expression of a dominant-negative form of TALK2 in comparison with that of wild-type TALK2. The sensitivities of TASK1-TALK2 tandem constructs to extracellular pH and halothane were characterized as a unique hybrid of TASK1 and TALK2. These results suggested that heterodimerization of TASK1 and TALK2 provides cells with the ability to make multiple responses to a variety of physiological and pharmacological stimuli.
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spelling pubmed-56346292017-10-30 Heterodimerization of two pore domain K(+) channel TASK1 and TALK2 in living heterologous expression systems Suzuki, Yoshiaki Tsutsumi, Kanako Miyamoto, Tatsuya Yamamura, Hisao Imaizumi, Yuji PLoS One Research Article Two-pore-domain K(+) (K(2P)) channels sense a wide variety of stimuli such as mechanical stress, inhalational anesthetics, and changes in extracellular pH or temperature. The K(2P) channel activity forms a background K(+) current and, thereby, contributes to resting membrane potentials. Six subfamilies including fifteen subtypes of K(2P) channels have been identified. Each K(2P) channel molecule with two pores consists of a homodimer of each subtype. In addition, a few heterodimers mainly within the same subfamilies have been found recently. In the present study, the possibility of heterodimerization between TASK1 (TWIK-Related Acid-Sensitive K(+) channel) and TALK2 (TWIK-Related Alkaline pH-Activated K(+) channel) was examined. These channels belong to separate subfamilies and show extremely different channel properties. Surprisingly, single molecular imaging analyses in this study using a total internal reflection microscope suggested the heterodimerization of TASK1 and TALK2 in a pancreatic cell line, QGP-1. This heterodimer was also detected using a bimolecular fluorescence complementation assay in a HEK293 heterologous expression system. Fluorescence resonance energy transfer analyses showed that the affinity between TASK1 and TALK2 appeared to be close to those of homodimers. Whole-cell patch-clamp recordings revealed that TASK1 currents in HEK293 cells were significantly attenuated by co-expression of a dominant-negative form of TALK2 in comparison with that of wild-type TALK2. The sensitivities of TASK1-TALK2 tandem constructs to extracellular pH and halothane were characterized as a unique hybrid of TASK1 and TALK2. These results suggested that heterodimerization of TASK1 and TALK2 provides cells with the ability to make multiple responses to a variety of physiological and pharmacological stimuli. Public Library of Science 2017-10-10 /pmc/articles/PMC5634629/ /pubmed/29016681 http://dx.doi.org/10.1371/journal.pone.0186252 Text en © 2017 Suzuki et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Suzuki, Yoshiaki
Tsutsumi, Kanako
Miyamoto, Tatsuya
Yamamura, Hisao
Imaizumi, Yuji
Heterodimerization of two pore domain K(+) channel TASK1 and TALK2 in living heterologous expression systems
title Heterodimerization of two pore domain K(+) channel TASK1 and TALK2 in living heterologous expression systems
title_full Heterodimerization of two pore domain K(+) channel TASK1 and TALK2 in living heterologous expression systems
title_fullStr Heterodimerization of two pore domain K(+) channel TASK1 and TALK2 in living heterologous expression systems
title_full_unstemmed Heterodimerization of two pore domain K(+) channel TASK1 and TALK2 in living heterologous expression systems
title_short Heterodimerization of two pore domain K(+) channel TASK1 and TALK2 in living heterologous expression systems
title_sort heterodimerization of two pore domain k(+) channel task1 and talk2 in living heterologous expression systems
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634629/
https://www.ncbi.nlm.nih.gov/pubmed/29016681
http://dx.doi.org/10.1371/journal.pone.0186252
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