ArticleThe Journal of biological chemistry2014
Tandem pore domain halothane-inhibited K+ channel subunits THIK1 and THIK2 assemble and form active channels.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Two pore domain THIK2 potassium channels regulate acute and chronic pain signaling.Pain reports · 2026Article
- A Forward Genetic Screen inbioRxiv : the preprint server for biology · 2026Article
- Swapped and non-swapped TRAAK states co-exist in membranes at a ratio influenced by temperature.Nature communications · 2026Article
- Mechanosensitive ion channels as novel targets in osteoporosis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Review
- Structure-Function Relationships of KAdvances in experimental medicine and biology · 2026Review
- Structure of the human KNature structural & molecular biology · 2025Article
- Gating mechanism of the two-pore-domain potassium channel THIK1.Nature structural & molecular biology · 2025Article
- Cryo-EM structure of the human THIK-1 K2P KNature structural & molecular biology · 2025Article
- Development of covalent chemogenetic KCell chemical biology · 2024Article
- Structure of the human KbioRxiv : the preprint server for biology · 2024Article
- Research progress of two-pore potassium channel in myocardial ischemia-reperfusion injury.Frontiers in physiology · 2024Review
- Development of covalent chemogenetic KbioRxiv : the preprint server for biology · 2023Article
- Cloxyquin activates hTRESK by allosteric modulation of the selectivity filter.Communications biology · 2023Article
- Evaluation of the Ion Channel Assembly in a Eukaryotic Cell-Free System Focusing on Two-Pore Domain Potassium Channels KInternational journal of molecular sciences · 2023Article
- Regulation of the two-pore domain potassium channel, THIK-1 and THIK-2, by G protein coupled receptors.PloS one · 2023Article
- A Direct Interaction between Cyclodextrins and TASK Channels Decreases the Leak Current in Cerebellar Granule Neurons.Biology · 2022Article
- Allosteric coupling between transmembrane segment 4 and the selectivity filter of TALK1 potassium channels regulates their gating by extracellular pH.The Journal of biological chemistry · 2022Article
- Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels.Current neuropharmacology · 2022Review
- Structural Insights into the Mechanisms and Pharmacology of KJournal of molecular biology · 2021Review
- Two-Pore Domain Potassium Channel in Neurological Disorders.The Journal of membrane biology · 2021Review
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6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite a high level of sequence homology, tandem pore domain halothane-inhibited K(+) channel 1 (THIK1) produces background K(+) currents, whereas THIK2 is silent. This lack of activity is due to a unique combination of intracellular retention and weak basal activity in the plasma membrane. Here, we designed THIK subunits containing dominant negative mutations (THIK1(DN) and THIK2(DN)). THIK2(DN) mutant inhibits THIK1 currents, whereas THIK1(DN) inhibits an activated form of THIK2 (THIK2-A155P-I158D). In situ proximity ligation assays and Förster/fluorescence resonance energy transfer (FRET) experiments support a physical association between THIK1 and THIK2. Next, we expressed covalent tandems of THIK proteins to obtain expression of pure heterodimers. Td-THIK1-THIK2 (where Td indicates tandem) produces K(+) currents of amplitude similar to Td-THIK1-THIK1 but with a noticeable difference in the current kinetics. Unlike Td-THIK2-THIK2 that is mainly detected in the endoplasmic reticulum, Td-THIK1-THIK2 distributes at the plasma membrane, indicating that THIK1 can mask the endoplasmic reticulum retention/retrieval motif of THIK2. Kinetics and unitary conductance of Td-THIK1-THIK2 are intermediate between THIK1 and THIK2. Altogether, these results show that THIK1 and THIK2 form active heteromeric channels, further expanding the known repertoire of K(+) channels.
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