ArticleProceedings of the National Academy of Sciences of the United States of America2007
Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed.
- 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
- The TWK-26/KCNK3 potassium channel and FLR-4 protein kinase coordinate nutrient absorption in the C. elegans intestine.Genetics · 2026Article
- Review
- Functional characterization of two KCND3 variants associated with SCA 19/22 ataxia in Latin American families.Biological research · 2025Article
- Ion occupancy of the selectivity filter controls opening of a cytoplasmic gate in the KNature communications · 2024Article
- 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
- The Dynamic Range of Acidity: Tracking Rules for the Unidirectional Penetration of Cellular Compartments.Chembiochem : a European journal of chemical biology · 2022Article
- A Direct Interaction between Cyclodextrins and TASK Channels Decreases the Leak Current in Cerebellar Granule Neurons.Biology · 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
- Endogenous pannexin1 channels form functional intercellular cell-cell channels with characteristic voltage-dependent properties.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural Insights into the Mechanisms and Pharmacology of KJournal of molecular biology · 2021Review
- Comparison of KHandbook of experimental pharmacology · 2021Article
- The Pharmacology of Two-Pore Domain Potassium Channels.Handbook of experimental pharmacology · 2021Article
- Article
- Elucidating the Structural Basis of the Intracellular pH Sensing Mechanism of TASK-2 KInternational journal of molecular sciences · 2020Article
- Bioinformatics in Latin America and SoIBio impact, a tale of spin-off and expansion around genomes and protein structures.Briefings in bioinformatics · 2019Article
- Mutation of a single residue promotes gating of vertebrate and invertebrate two-pore domain potassium channels.Nature communications · 2019Article
- Cardiovascular pharmacology of KNaunyn-Schmiedeberg's archives of pharmacology · 2018Article
- TRESK background potassium channel is not gated at the helix bundle crossing near the cytoplasmic end of the pore.PloS one · 2018Article
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6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Potassium channels share a common selectivity filter that determines the conduction characteristics of the pore. Diversity in K+ channels is given by how they are gated open. TASK-2, TALK-1, and TALK-2 are two-pore region (2P) KCNK K+ channels gated open by extracellular alkalinization. We have explored the mechanism for this alkalinization-dependent gating using molecular simulation and site-directed mutagenesis followed by functional assay. We show that the side chain of a single arginine residue (R224) near the pore senses pH in TASK-2 with an unusual pKa of 8.0, a shift likely due to its hydrophobic environment. R224 would block the channel through an electrostatic effect on the pore, a situation relieved by its deprotonation by alkalinization. A lysine residue in TALK-2 fulfills the same role but with a largely unchanged pKa, which correlates with an environment that stabilizes its positive charge. In addition to suggesting unified alkaline pH-gating mechanisms within the TALK subfamily of channels, our results illustrate in a physiological context the principle that hydrophobic environment can drastically modulate the pKa of charged amino acids within a protein.
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