ArticlePflugers Archiv : European journal of physiology2014
Breaking the silence: functional expression of the two-pore-domain potassium channel THIK-2.
Article in Pflugers Archiv : European journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Hippocampal Gene Expression in Zebra Finches Reveals Sex- and Subregion-Specific Topographies.eNeuro · 2026Article
- Structure-Function Relationships of KAdvances in experimental medicine and biology · 2026Review
- K2P channels as emerging therapeutic targets for pain: insights from functional studies and transcriptomic analyses.Frontiers in pharmacology · 2026Review
- Mechano- and Glucocorticoid-Sensitive TREK-1 Channels Regulate Conventional Outflow and Intraocular Pressure.Investigative ophthalmology & visual science · 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
- Structure of the human KNature structural & molecular biology · 2025Article
- Structure of the human KbioRxiv : the preprint server for biology · 2024Article
- Two-Pore-Domain Potassium (KCells · 2021Review
- 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
- The Pharmacology of Two-Pore Domain Potassium Channels.Handbook of experimental pharmacology · 2021Article
- KScience advances · 2020Article
- Ethanol acts on KCNK13 potassium channels in the ventral tegmental area to increase firing rate and modulate binge-like drinking.Neuropharmacology · 2019Article
- Regulatory Effect of General Anesthetics on Activity of Potassium Channels.Neuroscience bulletin · 2018Review
- Microglial Ramification, Surveillance, and Interleukin-1β Release Are Regulated by the Two-Pore Domain KNeuron · 2018Article
- The family of K2P channels: salient structural and functional properties.The Journal of physiology · 2015Review
- Silent but not dumb: how cellular trafficking and pore gating modulate expression of TWIK1 and THIK2.Pflugers Archiv : European journal of physiology · 2015Review
- Much more than a leak: structure and function of K₂p-channels.Pflugers Archiv : European journal of physiology · 2015Review
- The role of two-pore-domain background K⁺ (K₂p) channels in the thalamus.Pflugers Archiv : European journal of physiology · 2015Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
THIK-2 belongs to the 'silent' channels of the two-pore-domain potassium channel family. It is highly expressed in many nuclei of the brain but has so far resisted all attempts at functional expression. THIK-2 has a highly conserved 19-amino-acid region in its N terminus (residues 6-24 in the rat orthologue) that is missing in the closely related channel THIK-1. After deletion of this region (THIK-2(Δ6-24) mutant), functional expression of the channel was observed in Xenopus oocytes and in mammalian cell lines. The resulting potassium current showed outward rectification under physiological conditions and slight inward rectification with symmetrical high-K(+) solutions and could be inhibited by application of halothane or quinidine. Another THIK-2 mutant, in which the putative retention/retrieval signal RRR at positions 14-16 was replaced by AAA, produced a similar potassium current. Both mutants showed a distinct localisation to the surface membrane when tagged with green fluorescent protein and expressed in a mammalian cell line, whereas wild-type THIK-2 was mainly localised to the endoplasmic reticulum. These findings suggest that deletion of the retention/retrieval signal RRR enabled transport of THIK-2 channels to the surface membrane. Combining the mutation THIK-2(Δ6-24) with a mutation in the pore cavity (rat THIK-2(I158G)) gave rise to a 12-fold increase in current amplitude, most likely due to an increase in open probability. In conclusion, the characteristics of THIK-2 channels can be analysed in heterologous expression systems by using trafficking and/or gating mutants. The possible mechanisms that enable THIK-2 expression at the surface membrane in vivo remain to be determined.
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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.