ArticleProceedings of the National Academy of Sciences of the United States of America2009
Extracellular acidification exerts opposite actions on TREK1 and TREK2 potassium channels via a single conserved histidine residue.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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91 citing papers in PubMed, 149 citations in OpenAlex.
- Temperature and pH-dependent potassium currents of muscles of the stomatogastric nervous system of the crab,iScience · 2026Article
- Joint Acidosis and Acid-Sensing Receptors and Ion Channels in Osteoarthritis Pathobiology and Therapy.Cells · 2025Review
- Temperature and pH-dependent Potassium Currents of Muscles of the Stomatogastric Nervous System of the Crab,bioRxiv : the preprint server for biology · 2025Article
- Mechanosensing of Shear Stress and Uterine Spiral Artery Remodeling by Invasive Trophoblasts in Early Pregnancy.International journal of molecular sciences · 2025Review
- Increasing Temperature Activates TREK Potassium Currents in Vagal Afferent Neurons from the Nodose Ganglion.International journal of molecular sciences · 2025Article
- Cell Settling, Migration, and Stochastic Cancer Gene Expression Suggest Potassium Membrane Flux May Initiate pH Reversal.Biomolecules · 2025Article
- Structure of the human KNature structural & molecular biology · 2025Article
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- 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
- Development of covalent chemogenetic KbioRxiv : the preprint server for biology · 2023Article
- Mechanism of external K+ sensitivity of KCNQ1 channels.The Journal of general physiology · 2023Article
- Synergistic effects of agonists and two-pore-domain potassium channels on secretory responses of human pancreatic duct cells Capan-1.Pflugers Archiv : European journal of physiology · 2023Article
- Membrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1.Nature communications · 2023Article
- Multiple Effects of Echinochrome A on Selected Ion Channels Implicated in Skin Physiology.Marine drugs · 2023Article
- 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
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31 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Mechanosensitive K(+) channels TREK1 and TREK2 form a subclass of two P-domain K(+) channels. They are potently activated by polyunsaturated fatty acids and are involved in neuroprotection, anesthesia, and pain perception. Here, we show that acidification of the extracellular medium strongly inhibits TREK1 with an apparent pK near to 7.4 corresponding to the physiological pH. The all-or-none effect of pH variation is steep and is observed within one pH unit. TREK2 is not inhibited but activated by acidification within the same range of pH, despite its close homology with TREK1. A single conserved residue, H126 in TREK1 and H151 in TREK2, is involved in proton sensing. This histidine is located in the M1P1 extracellular loop preceding the first P domain. The differential effect of acidification, that is, activation for TREK2 and inhibition for TREK1, involves other residues located in the P2M4 loop, linking the second P domain and the fourth membrane-spanning segment. Structural modeling of TREK1 and TREK2 and site-directed mutagenesis strongly suggest that attraction or repulsion between the protonated side chain of histidine and closely located negatively or positively charged residues in P2M4 control outer gating of these channels. The differential sensitivity of TREK1 and TREK2 to external pH variations discriminates between these two K(+) channels that otherwise share the same regulations by physical and chemical stimuli, and by hormones and neurotransmitters.
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