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

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Protein Multimerization*; Insulin-Secreting Cells/*metabolism ; Membrane Potentials/*physiology ; Nerve Tissue Proteins/*genetics ; Potassium Channels, Tandem Pore Domain/*genetics; Anesthetics, Inhalation/pharmacology ; Cell Line, Tumor ; Fluorescence Resonance Energy Transfer ; Gene Expression ; HEK293 Cells ; Halothane/pharmacology ; Humans ; Hydrogen-Ion Concentration ; Insulin-Secreting Cells/cytology ; Insulin-Secreting Cells/drug effects ; Membrane Potentials/drug effects ; Molecular Imaging ; Nerve Tissue Proteins/agonists ; Nerve Tissue Proteins/chemistry ; Nerve Tissue Proteins/metabolism ; Patch-Clamp Techniques ; Potassium Channels, Tandem Pore Domain/agonists ; Potassium Channels, Tandem Pore Domain/antagonists & inhibitors ; Potassium Channels, Tandem Pore Domain/chemistry ; Potassium Channels, Tandem Pore Domain/metabolism ; Protein Domains ; Single Molecule Imaging ; Transgenes

Two-pore-domain K+ (K2P) channels sense a wide variety of stimuli such as mechanical stress, inhalational anesthetics, and changes in extracellular pH or temperature. The K2P channel activity forms a background K+ current and, thereby, contributes to resting membrane potentials. Six subfamilies including fifteen subtypes of K2P channels have been identified. Each K2P 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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0 (Anesthetics, Inhalation)
0 (KCNK17 protein, human)
0 (Nerve Tissue Proteins)
0 (Potassium Channels, Tandem Pore Domain)
1HQ3YCN4GS (potassium channel subfamily K member 3)
UQT9G45D1P (Halothane)

Date Created: 20171011 Date Completed: 20171019 Latest Revision: 20181202

20231215

PMC5634629

10.1371/journal.pone.0186252

29016681