ArticleThe Journal of biological chemistry2013
Silencing of the tandem pore domain halothane-inhibited K+ channel 2 (THIK2) relies on combined intracellular retention and low intrinsic activity at the plasma membrane.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Two pore domain THIK2 potassium channels regulate acute and chronic pain signaling.Pain reports · 2026Article
- Gating crosstalk in potassium channels.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Forward Genetic Screen inbioRxiv : the preprint server for biology · 2026Article
- K2P channels as emerging therapeutic targets for pain: insights from functional studies and transcriptomic analyses.Frontiers in pharmacology · 2026Review
- Inhibitory effect of 17β-estradiol on the THIK-1 channel.PloS one · 2026Article
- Cryo-EM structure of the human THIK-1 K2P KNature structural & molecular biology · 2025Article
- Structure of the human KNature structural & molecular biology · 2025Article
- Gating mechanism of the two-pore-domain potassium channel THIK1.Nature structural & molecular biology · 2025Article
- Structure of the human KbioRxiv : the preprint server for biology · 2024Article
- Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation.Nature communications · 2024Article
- Differential contribution of THIK-1 KJournal of neuroinflammation · 2024Article
- Regulation of the two-pore domain potassium channel, THIK-1 and THIK-2, by G protein coupled receptors.PloS one · 2023Article
- Two-Pore-Domain Potassium (KCells · 2021Review
- The Pharmacology of Two-Pore Domain Potassium Channels.Handbook of experimental pharmacology · 2021Article
- Mutation of a single residue promotes gating of vertebrate and invertebrate two-pore domain potassium channels.Nature communications · 2019Article
- Ethanol acts on KCNK13 potassium channels in the ventral tegmental area to increase firing rate and modulate binge-like drinking.Neuropharmacology · 2019Article
- TALK-1 channels control β cell endoplasmic reticulum CaScience signaling · 2017Article
- Recombinant tandem of pore-domains in a Weakly Inward rectifying KScientific reports · 2017Article
- The family of K2P channels: salient structural and functional properties.The Journal of physiology · 2015Review
- Much more than a leak: structure and function of K₂p-channels.Pflugers Archiv : European journal of physiology · 2015Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tandem pore domain halothane-inhibited K(+) channel 1 (THIK1) produces background K(+) currents. Despite 62% amino acid identity with THIK1, THIK2 is not active upon heterologous expression. Here, we show that this apparent lack of activity is due to a unique combination of retention in the endoplasmic reticulum and low intrinsic channel activity at the plasma membrane. A THIK2 mutant containing a proline residue (THIK2-A155P) in its second inner helix (M2) produces K(+)-selective currents with properties similar to THIK1, including inhibition by halothane and insensitivity to extracellular pH variations. Another mutation in the M2 helix (I158D) further increases channel activity and affects current kinetics. We also show that the cytoplasmic amino-terminal region of THIK2 (Nt-THIK2) contains an arginine-rich motif (RRSRRR) that acts as a retention/retrieval signal. Mutation of this motif in THIK2 induces a relocation of the channel to the plasma membrane, resulting in measurable currents, even in the absence of mutations in the M2 helix. Cell surface delivery of a Nt-THIK2-CD161 chimera is increased by mutating the arginines of the retention motif but also by converting the serine embedded in this motif to aspartate, suggesting a phosphorylation-dependent regulation of THIK2 trafficking.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.