ArticleThe Journal of general physiology2022
The versatile regulation of K2P channels by polyanionic lipids of the phosphoinositide and fatty acid metabolism.
Article in The Journal of general physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- The diabetes-associated KDiabetologia · 2026Article
- Swapped and non-swapped TRAAK states co-exist in membranes at a ratio influenced by temperature.Nature communications · 2026Article
- Inhibitory effect of 17β-estradiol on the THIK-1 channel.PloS one · 2026Article
- Membrane-forming phospholipids allosterically modulate native-state prolyl isomerization in a CNG channel.Protein science : a publication of the Protein Society · 2025Article
- Atomistic mechanism of noncanonical voltage gating in KScience advances · 2025Article
- Cryo-EM structure of the human THIK-1 K2P KNature structural & molecular biology · 2025Article
- Gating mechanism of the two-pore-domain potassium channel THIK1.Nature structural & molecular biology · 2025Article
- The cryo-EM structure and physical basis for anesthetic inhibition of the THIK1 K2P channel.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ion channels of cold transduction and transmission.The Journal of general physiology · 2024Review
- PIP2 inhibits pore opening of the cyclic nucleotide-gated channel SthK.Nature communications · 2024Article
- Ion occupancy of the selectivity filter controls opening of a cytoplasmic gate in the KNature communications · 2024Article
- Atomistic mechanism of coupling between cytosolic sensor domain and selectivity filter in TREK K2P channels.Nature communications · 2024Article
- Disrupted Endoplasmic Reticulum CaBiology · 2024Review
- Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A.Nature communications · 2023Article
- Potassium Ion Channels in Glioma: From Basic Knowledge into Therapeutic Applications.Membranes · 2023Review
- Membrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1.Nature communications · 2023Article
- Regulation of the two-pore domain potassium channel, THIK-1 and THIK-2, by G protein coupled receptors.PloS one · 2023Article
- Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea.Nature genetics · 2022Article
- Transition between conformational states of the TREK-1 K2P channel promoted by interaction with PIPBiophysical journal · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Work over the past three decades has greatly advanced our understanding of the regulation of Kir K+ channels by polyanionic lipids of the phosphoinositide (e.g., PIP2) and fatty acid metabolism (e.g., oleoyl-CoA). However, comparatively little is known regarding the regulation of the K2P channel family by phosphoinositides and by long-chain fatty acid-CoA esters, such as oleoyl-CoA. We screened 12 mammalian K2P channels and report effects of polyanionic lipids on all tested channels. We observed activation of members of the TREK, TALK, and THIK subfamilies, with the strongest activation by PIP2 for TRAAK and the strongest activation by oleoyl-CoA for TALK-2. By contrast, we observed inhibition for members of the TASK and TRESK subfamilies. Our results reveal that TASK-2 channels have both activatory and inhibitory PIP2 sites with different affinities. Finally, we provided evidence that PIP2 inhibition of TASK-1 and TASK-3 channels is mediated by closure of the recently identified lower X-gate as critical mutations within the gate (i.e., L244A, R245A) prevent PIP2-induced inhibition. Our findings establish that K+ channels of the K2P family are highly sensitive to polyanionic lipids, extending our knowledge of the mechanisms of lipid regulation and implicating the metabolism of these lipids as possible effector pathways to regulate K2P channel activity.
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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 Socratic graph.