ArticleThe Journal of biological chemistry2010
Separate gating mechanisms mediate the regulation of K2P potassium channel TASK-2 by intra- and extracellular pH.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 1 citations in OpenAlex.
- Mechanisms of intracellular pH gating and local anesthetic inhibition of the two-pore domain KProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Insights into the structure and modulation of human TWIK-2.Nature communications · 2026Article
- Structure-Function Relationships of KAdvances in experimental medicine and biology · 2026Review
- Cell Settling, Migration, and Stochastic Cancer Gene Expression Suggest Potassium Membrane Flux May Initiate pH Reversal.Biomolecules · 2025Article
- Research progress of two-pore potassium channel in myocardial ischemia-reperfusion injury.Frontiers in physiology · 2024Review
- Thalamocortical circuits in generalized epilepsy: Pathophysiologic mechanisms and therapeutic targets.Neurobiology of disease · 2023Review
- 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
- Criteria for central respiratory chemoreceptors: experimental evidence supporting current candidate cell groups.Frontiers in physiology · 2023Review
- TWIK-related acid-sensitive KiScience · 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
- The versatile regulation of K2P channels by polyanionic lipids of the phosphoinositide and fatty acid metabolism.The Journal of general physiology · 2022Article
- Article
- Structural Insights into the Mechanisms and Pharmacology of KJournal of molecular biology · 2021Review
- The Pharmacology of Two-Pore Domain Potassium Channels.Handbook of experimental pharmacology · 2021Article
- Article
- Connexin26 mediates COCommunications biology · 2020Article
- The role of TASK-2 channels in COAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Intracellular acidification facilitates receptor-operated TRPC4 activation through PLCδ1 in a CaThe Journal of physiology · 2020Article
- Elucidating the Structural Basis of the Intracellular pH Sensing Mechanism of TASK-2 KInternational journal of molecular sciences · 2020Article
- Phosphatidylinositol (4,5)-bisphosphate dynamically regulates the KScientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TASK-2 (KCNK5 or K(2P)5.1) is a background K(+) channel that is opened by extracellular alkalinization and plays a role in renal bicarbonate reabsorption and central chemoreception. Here, we demonstrate that in addition to its regulation by extracellular protons (pH(o)) TASK-2 is gated open by intracellular alkalinization. The following pieces of evidence suggest that the gating process controlled by intracellular pH (pH(i)) is independent from that under the command of pH(o). It was not possible to overcome closure by extracellular acidification by means of intracellular alkalinization. The mutant TASK-2-R224A that lacks sensitivity to pH(o) had normal pH(i)-dependent gating. Increasing extracellular K(+) concentration acid shifts pH(o) activity curve of TASK-2 yet did not affect pH(i) gating of TASK-2. pH(o) modulation of TASK-2 is voltage-dependent, whereas pH(i) gating was not altered by membrane potential. These results suggest that pH(o), which controls a selectivity filter external gate, and pH(i) act at different gating processes to open and close TASK-2 channels. We speculate that pH(i) regulates an inner gate. We demonstrate that neutralization of a lysine residue (Lys(245)) located at the C-terminal end of transmembrane domain 4 by mutation to alanine abolishes gating by pH(i). We postulate that this lysine acts as an intracellular pH sensor as its mutation to histidine acid-shifts the pH(i)-dependence curve of TASK-2 as expected from its lower pK(a). We conclude that intracellular pH, together with pH(o), is a critical determinant of TASK-2 activity and therefore of its physiological function.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.