ArticleThe Journal of general physiology2010
Fatty acid modulation and polyamine block of GluK2 kainate receptors analyzed by scanning mutagenesis.
Article in The Journal of general physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 19 citations in OpenAlex.
- Intracellular Spermine Is a Key Player in GSG1L's Regulation of Calcium-Permeable AMPAR Channel Conductance and Recovery from Desensitization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Structural basis of AMPA receptor inhibition by trans-4-butylcyclohexane carboxylic acid.British journal of pharmacology · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Interplay between Gating and Block of Ligand-Gated Ion Channels.Brain sciences · 2020Review
- Cadmium opens GluK2 kainate receptors with cysteine substitutions at the M3 helix bundle crossing.The Journal of general physiology · 2019Article
- Polyamine-mediated channel block of ionotropic glutamate receptors and its regulation by auxiliary proteins.The Journal of biological chemistry · 2018Review
- Article
- Stargazin and cornichon-3 relieve polyamine block of AMPA receptors by enhancing blocker permeation.The Journal of general physiology · 2018Article
- The Challenge of Interpreting Glutamate-Receptor Ion-Channel Structures.Biophysical journal · 2017Review
- Glutamate receptor pores.The Journal of physiology · 2015Review
- Regulation of Ion Channel and Transporter Function Through RNA Editing.Current issues in molecular biology · 2015Review
- Q/R site interactions with the M3 helix in GluK2 kainate receptor channels revealed by thermodynamic mutant cycles.The Journal of general physiology · 2013Article
- Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca²⁺-dependent K⁺ channels.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary?The Journal of nutrition · 2012Review
- Emerging models of glutamate receptor ion channel structure and function.Structure (London, England : 1993) · 2011Review
- Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation.Current opinion in neurobiology · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
RNA editing of kainate receptor subunits at the Q/R site determines their susceptibility to inhibition by cis-unsaturated fatty acids as well as block by cytoplasmic polyamines. Channels comprised of unedited (Q) subunits are strongly blocked by polyamines, but insensitive to fatty acids, such as arachidonic acid (AA) and docosahexaenoic acid (DHA), whereas homomeric edited (R) channels resist polyamine block but are inhibited by AA and DHA. In the present study, we have analyzed fatty acid modulation of whole-cell currents mediated by homomeric recombinant GluK2 (formerly GluR6) channels with individual residues in the pore-loop, M1 and M3 transmembrane helices replaced by scanning mutagenesis. Our results define three abutting surfaces along the M1, M2, and M3 helices where gain-of-function substitutions render GluK2(Q) channels susceptible to fatty acid inhibition. In addition, we identify four locations in the M3 helix (F611, L614, S618, and T621) at the level of the central cavity where Arg substitution increases relative permeability to chloride and eliminates polyamine block. Remarkably, for two of these positions, L614R and S618R, exposure to fatty acids reduces the apparent chloride permeability and potentiates whole-cell currents approximately 5 and 2.5-fold, respectively. Together, our results suggest that AA and DHA alter the orientation of M3 in the open state, depending on contacts at the interface between M1, M2, and M3. Moreover, our results demonstrate the importance of side chains within the central cavity in determining ionic selectivity and block by cytoplasmic polyamines despite the inverted orientation of GluK2 as compared with potassium channels and other pore-loop family members.
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.