ArticleThe Journal of biological chemistry2011
Characterization of a binding site for anionic phospholipids on KCNQ1.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 48 citations in OpenAlex.
- Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating.Cell research · 2025Article
- Phosphatidylinositol 4,5-bisphosphate activation mechanism of human KCNQ5.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Membrane pools of phosphatidylinositol-4-phosphate regulate KCNQ1/KCNE1 membrane expression.Communications biology · 2021Article
- From Bench to Biomolecular Simulation: Phospholipid Modulation of Potassium Channels.Journal of molecular biology · 2021Review
- A PIPCommunications biology · 2020Article
- Physical and functional interaction sites in cytoplasmic domains of KCNQ1 and KCNE1 channel subunits.American journal of physiology. Heart and circulatory physiology · 2020Article
- Modulation of KFrontiers in pharmacology · 2020Article
- Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome.Frontiers in pharmacology · 2020Review
- Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes.Frontiers in physiology · 2020Review
- Investigating the Complex Arrhythmic Phenotype Caused by the Gain-of-Function Mutation KCNQ1-G229D.Frontiers in physiology · 2019Article
- Phosphatidylinositol 4,5-bisphosphate (PIPThe Journal of biological chemistry · 2018Article
- Reduced axonal surface expression and phosphoinositide sensitivity in KNeurobiology of disease · 2018Article
- CaChannels (Austin, Tex.) · 2017Article
- Regulation of KCNQ/Kv7 family voltage-gated KBiochimica et biophysica acta. Biomembranes · 2017Review
- Competition of calcified calmodulin N lobe and PIP2 to an LQT mutation site in Kv7.1 channel.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Phosphatidylinositol-4,5-bisphosphate is required for KCNQ1/KCNE1 channel function but not anterograde trafficking.PloS one · 2017Article
- Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate.Scientific reports · 2016Article
- Cardiac Delayed Rectifier Potassium Channels in Health and Disease.Cardiac electrophysiology clinics · 2016Review
- Voltage-Dependent Gating: Novel Insights from KCNQ1 Channels.Biophysical journal · 2016Review
- PIP₂-dependent coupling is prominent in Kv7.1 due to weakened interactions between S4-S5 and S6.Scientific reports · 2015Article
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 1 institution in 1 country.
Funding
Abstract
The KCNQ family of potassium channels underlie a repolarizing K(+) current in the heart and the M-current in neurones. The assembly of KCNQ1 with KCNE1 generates the delayed rectifier current I(Ks) in the heart. Characteristically these channels are regulated via G(q/11)-coupled receptors and the inhibition seen after phospholipase C activation is now thought to occur from membrane phosphatidylinositol (4,5)-bisphosphate (PIP(2)) depletion. It is not clear how KCNQ1 recognizes PIP(2) and specifically which residues in the channel complex are important. Using biochemical techniques we identify a cluster of basic residues namely, Lys-354, Lys-358, Arg-360, and Lys-362, in the proximal C terminus as being involved in binding anionic phospholipids. The mutation of specific residues in combination, to alanine leads to the loss of binding to phosphoinositides. Functionally, the introduction of these mutations into KCNQ1 leads to shifts in the voltage dependence of channel activation toward depolarized potentials and reductions in current density. Additionally, the biophysical effects of the charge neutralizing mutations, which disrupt phosphoinositide binding, mirror the effects we see on channel function when we deplete cellular PIP(2) levels through activation of a G(q/11)-coupled receptor. Conversely, the addition of diC8-PIP(2) to the wild-type channel, but not a PIP(2) binding-deficient mutant, acts to shift the voltage dependence of channel activation toward hyperpolarized potentials and increase current density. In conclusion, we use a combined biochemical and functional approach to identify a cluster of basic residues important for the binding and action of anionic phospholipids on the KCNQ1/KCNE1 complex.
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.