Affinage

KCNQ2

Potassium voltage-gated channel subfamily KQT member 2 · UniProt O43526

Length
872 aa
Mass
95.8 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNQ2 encodes the Kv7.2 voltage-gated K+ channel subunit that, together with KCNQ3 (and KCNQ5), generates the neuronal M-current controlling excitability and action-potential firing; mouse knockout and the Szt1 C-terminal deletion eliminate or reduce M-current, impair spike-frequency adaptation, and produce convulsant hypersensitivity, establishing KCNQ2 as a brake on neuronal excitability (PMID:10854243, PMID:16481438). Kv7.2 assembles with Kv7.3 through a C-terminal A-domain interaction into a predominantly 2:2 heterotetramer, and co-assembly markedly increases surface expression of both subunits (PMID:10788442, PMID:12640002, PMID:22334706); KCNQ2 also forms KCNQ3-independent heteromers with KCNQ5 in native brain (PMID:35320039). The channel is anchored at axon initial segments and nodes of Ranvier alongside Nav channels via ankyrin-G, an interaction augmented by CK2 phosphorylation, with FGF14 acting as an organizer that bridges Nav1.6 and KCNQ2 at the AIS (PMID:14762142, PMID:25998125, PMID:27994149). Calmodulin binds constitutively to two C-terminal IQ-like motifs and is required for ER exit, heteromeric assembly, AIS targeting, and current generation; loss of CaM binding causes ER retention (PMID:12223552, PMID:17993630, PMID:24333508). Channel opening requires membrane PIP2, and M-current is suppressed when Gq-coupled muscarinic receptors activate PLC to hydrolyze PIP2, with PIP2 hydrolysis as the rate-limiting step (PMID:15173220, PMID:19332618). Activity is further tuned by a tethered CK2/PP1 module (CK2 phosphorylates CaM to strengthen binding and PIP2 resistance), PKC phosphorylation at S559 driving neurotransmitter-induced suppression, a serine cluster phosphorylated by CDK5/p38/CaMKII/PKA that sets PIP2 sensitivity, Nedd4-2 ubiquitination, GSK3β phosphorylation, and SUMOylation that impairs PIP2 and CaM binding (PMID:24627475, PMID:27621207, PMID:30146722, PMID:17322297, PMID:16733521, PMID:34509475). Loss-of-function mutations cause neonatal epilepsy and encephalopathy through haploinsufficiency, dominant-negative current reduction, or mislocalization away from the AIS, while gain-of-function voltage-sensor mutations that stabilize the activated state also cause epilepsy with cell-type-specific effects on excitability (PMID:10854243, PMID:24318194, PMID:26007637, PMID:25740509, PMID:37607817).

Mechanistic history

Synthesis pass · year-by-year structured walk · 34 steps
  1. 2000 High

    Established that KCNQ2 is genetically required for the neuronal M-current in vivo and that reduced dosage causes hyperexcitability, defining its physiological role as an excitability brake.

    Evidence Homozygous and heterozygous Kcnq2 knockout mice with pentylenetetrazole seizure-threshold assay

    PMID:10854243

    Open questions at the time
    • Did not resolve subcellular site of M-current control
    • Homozygous lethality limited adult analysis
  2. 2000 High

    Showed that KCNQ2/KCNQ3 co-assembly drives the large M-current chiefly by boosting surface expression, explaining why both subunits are needed for robust current.

    Evidence Single-channel recording and surface biotinylation in Xenopus oocytes, with a BFNC C-terminal truncation mutant

    PMID:10788442

    Open questions at the time
    • Trafficking machinery mediating the surface boost unidentified
    • Did not define assembly stoichiometry
  3. 2002 High

    Identified calmodulin as a constitutive auxiliary subunit essential for current generation, linking the channel to Ca2+ signaling.

    Evidence Yeast two-hybrid, co-IP from mouse brain, CHO electrophysiology, CaM-motif mutagenesis

    PMID:12223552

    Open questions at the time
    • Mechanism by which CaM enables current not yet resolved (later shown to be trafficking)
    • Ca2+ vs apoCaM roles unclear at this stage
  4. 2003 High

    Mapped the C-terminal A-domain as the determinant of KCNQ2/KCNQ3 heteromeric assembly, defining the molecular basis of subunit selectivity.

    Evidence Chimeric channel construction and two-microelectrode voltage clamp in oocytes

    PMID:12640002

    Open questions at the time
    • No structural model of the interface
    • Stoichiometry not determined
  5. 2004 High

    Localized KCNQ2 to axon initial segments and nodes of Ranvier in complex with ankyrin-G and Nav channels, placing M-current control at the spike-initiation zone.

    Evidence Immunohistochemistry, co-IP from brain, pharmacological electrophysiology in nerves

    PMID:14762142

    Open questions at the time
    • AnkG binding site and regulation not defined
    • Did not establish how channel:Nav ratio is set
  6. 2004 High

    Reconstituted the Gq-PLC-PIP2 cascade for muscarinic M-current suppression, establishing PIP2 depletion as the primary suppression mechanism.

    Evidence Whole-cell patch and GFP-PH PIP2 probe in tsA-201 cells with G-protein and RGS2 manipulations

    PMID:15173220

    Open questions at the time
    • Rate-limiting step not yet pinpointed
    • PIP2 binding residues on the channel unmapped
  7. 2006 High

    Demonstrated in native CA1 neurons that KCNQ2 supplies the M-current regulating spike-frequency adaptation, connecting molecular function to firing control.

    Evidence Perforated-patch electrophysiology in Szt1 mutant mouse hippocampal slices

    PMID:16481438

    Open questions at the time
    • Did not address other afterhyperpolarization currents
    • Behavioral consequences not tested
  8. 2006 Medium

    Identified additional regulatory inputs (PP2A-Bgamma enhancement, GSK3beta inhibition) and dominant-negative truncation variants, broadening the post-translational regulatory landscape.

    Evidence Yeast two-hybrid, heterologous electrophysiology, GSK3beta phosphorylation assay

    PMID:16733521

    Open questions at the time
    • Single lab with limited biochemical follow-up
    • GSK3beta phospho-sites not mapped
    • Physiological relevance untested
  9. 2007 High

    Showed CaM binding controls ER export, mechanistically explaining the requirement for CaM in current generation and a BFNC mutation's loss of function.

    Evidence Live-cell imaging, subcellular fractionation, CaM overexpression/sequestration in transfected cells

    PMID:17993630

    Open questions at the time
    • Did not address AIS targeting specifically
    • Quality-control machinery sensing CaM occupancy unknown
  10. 2007 High

    Established Nedd4-2 as a direct ubiquitin ligase reducing KCNQ2/3 current, adding degradative control over channel abundance.

    Evidence GST pulldown, co-IP, ubiquitination assay and electrophysiology in oocytes

    PMID:17322297

    Open questions at the time
    • In vivo relevance of Nedd4-2 regulation not shown
    • Ubiquitination sites not mapped
  11. 2007 Medium

    Distinguished receptor-specific M-current suppression mechanisms, showing bradykinin uses Ca2+/IP3 or PIP2 depletion depending on PIP2 supply.

    Evidence Tubby-PIP2 sensor imaging in sympathetic neurons with pharmacological perturbation

    PMID:17395626 PMID:17447081

    Open questions at the time
    • Single lab
    • Relative contribution in intact circuits unclear
  12. 2008 High

    Expanded KCNQ2's contribution to the medium and slow afterhyperpolarization currents in hippocampal neurons, linking it to spike-train regulation.

    Evidence Patch clamp in KCNQ2/3 knockout hippocampal slices with KCNQ pharmacology

    PMID:19060215

    Open questions at the time
    • Hippocalcin link not mechanistically resolved
    • Did not separate KCNQ2 vs KCNQ3 contributions fully
  13. 2009 High

    Identified PIP2 hydrolysis as the rate-limiting step of muscarinic suppression, refining the kinetic model of M-current control.

    Evidence Pairwise FRET of each signaling step plus electrophysiology and PLC overexpression

    PMID:19332618

    Open questions at the time
    • Channel PIP2 affinity determinants not mapped here
    • In vivo kinetics not addressed
  14. 2012 High

    Determined that Kv7.2/7.3 assembles predominantly as a 2:2 tetramer with non-fixed subunit arrangement, defining channel architecture.

    Evidence Atomic force microscopy of antibody-decorated isolated channel complexes

    PMID:22334706

    Open questions at the time
    • Functional consequence of variable arrangement unresolved
    • No atomic structure
  15. 2013 High

    Revealed that calmodulin orchestrates heteromeric assembly and AIS targeting, integrating the trafficking and assembly roles of CaM.

    Evidence Co-IP, AIS immunofluorescence in neurons, CaM rescue and mutagenesis

    PMID:24333508

    Open questions at the time
    • How CaM couples to AIS anchoring machinery unclear
    • Apo- vs Ca2+-CaM roles not fully separated
  16. 2014 High

    Showed a tethered CK2/PP1 module sets channel activity, with CK2 phosphorylating CaM to strengthen binding and confer PIP2-depletion resistance.

    Evidence Co-IP of CK2/PP1, PP1-motif mutagenesis, CaM phosphorylation assay, electrophysiology in HEK and SCG neurons

    PMID:24627475

    Open questions at the time
    • Stoichiometry of the tethered module not defined
    • In vivo role of PP1 tethering untested
  17. 2014 High

    Defined AnkG-mediated anchoring with CK2-augmented binding and a splice-regulated mechanism setting the Nav:KCNQ ratio at the distal AIS.

    Evidence Pulldowns, co-IP, AnkG repeat mutagenesis, in vitro CK2 phosphorylation

    PMID:25998125

    Open questions at the time
    • Structural basis of distinct KCNQ2 vs KCNQ3 anchor sites incomplete
    • Regulation of splice choice in vivo unknown
  18. 2014 High

    Demonstrated a peripheral sensory role: conditional Kcnq2 deletion increases sensory neuron excitability and produces hyperalgesia and allodynia.

    Evidence Cre-Lox conditional knockout, DRG patch clamp, nociception behavior

    PMID:24687876

    Open questions at the time
    • Molecular trigger of pain phenotype not dissected
    • Did not test M-current modulators in vivo
  19. 2015 High

    Showed gain-of-function voltage-sensor mutations stabilize the activated state and cause epilepsy by reducing interneuron output, complicating the loss-of-function paradigm.

    Evidence Electrophysiology, disulfide trapping, structural and circuit modeling

    PMID:25740509

    Open questions at the time
    • Circuit prediction not validated in native tissue at this stage
    • No high-resolution structure of the activated state
  20. 2014 High

    Distinguished dominant-negative encephalopathy mutations from haploinsufficient BFNC mutations and showed retigabine partial rescue, informing genotype-phenotype severity.

    Evidence Two-microelectrode voltage clamp and surface biotinylation across 7 mutations

    PMID:24318194

    Open questions at the time
    • Native neuronal consequences not assessed
    • Mechanism of dominant-negative suppression not structurally defined
  21. 2015 High

    Established subcellular mislocalization (somatodendritic vs AIS) as a determinant of disease severity, beyond simple current reduction.

    Evidence Patch clamp, Western blot, AIS immunofluorescence comparing A294V and A294G in neurons

    PMID:26007637

    Open questions at the time
    • Trafficking step disrupted by A294V not identified
    • Single residue comparison
  22. 2016 High

    Mapped a serine cluster phosphorylated by CDK5/p38/CaMKII/PKA that tunes channel PIP2 sensitivity and receptor-specific suppression.

    Evidence Phosphoproteomics, in vitro kinase assay with purified C-terminus, Dr-VSP PIP2 assay, mutagenesis

    PMID:27621207

    Open questions at the time
    • Which kinase dominates in vivo unclear
    • Did not test cluster phospho-state in disease
  23. 2016 Medium

    Showed gain-of-function gating mutations (V175L, R198Q) cause encephalopathy without altering AIS localization, establishing gating change as a sufficient pathogenic mechanism.

    Evidence Patch clamp in CHO cells and AIS immunofluorescence in neurons

    PMID:27030113 PMID:27861786

    Open questions at the time
    • Single mutations per study
    • Circuit-level excitability not tested
  24. 2016 High

    Defined channel surface dynamics: AIS Kv7.2/7.3 is highly stable but undergoes calpain-dependent excitotoxic endocytosis under glutamate load, linking M-channels to excitotoxicity.

    Evidence Live imaging with SEP-TAC-Kv7.3 phluorin chimera and pharmacological dissection in hippocampal neurons

    PMID:26888935

    Open questions at the time
    • In vivo relevance to seizure-induced injury not directly shown here
    • Endocytic adaptor machinery undefined
  25. 2016 Medium

    Identified FGF14 as a positive regulator and AIS organizer that bridges Nav1.6 and KCNQ2, coordinating co-localization of the two channel classes.

    Evidence siRNA knockdown, co-IP, AIS immunofluorescence, patch clamp

    PMID:27994149

    Open questions at the time
    • Single study
    • Structural basis of the bridging not resolved
  26. 2018 High

    Linked CaM-binding-helix encephalopathy mutations to reduced surface expression, with M518V driving CaM loss, ubiquitination, and proteasomal degradation, and exposing novel PIP2 residues.

    Evidence Surface biotinylation, CaM co-IP, ubiquitination/proteasome assays, patch clamp, neuronal imaging

    PMID:30008368

    Open questions at the time
    • Ligase responsible for M518V ubiquitination not identified
    • Did not test rescue in vivo
  27. 2018 High

    Established PKC phosphorylation at S559 as a key driver of neurotransmitter-induced M-current suppression with direct seizure and neuroprotection consequences in vivo.

    Evidence Kv7.2(S559A) knock-in mice, patch clamp, pilocarpine SE, histology, EEG

    PMID:30146722

    Open questions at the time
    • Upstream receptor specificity for S559 not fully resolved
    • Structural impact of phosphorylation unknown
  28. 2020 Medium

    Mapped helix B and pore residues (K552T, R553L, L268F) critical for CaM binding, axonal enrichment, and PIP2 potentiation, refining the structural map of regulatory residues.

    Evidence Mutation mapping, structural modeling, MD simulation, patch clamp and surface/internalization assays in neurons

    PMID:32179837

    Open questions at the time
    • Single lab
    • MD-predicted PIP2 contacts not experimentally confirmed structurally
  29. 2021 Medium

    Showed SUMOylation negatively regulates the channel by impairing PIP2 and CaM binding and that SENP2 deSUMOylation maintains M-current, adding a SUMO-based regulatory layer.

    Evidence SENP2 knockout mice, co-IP, SUMO-site mutagenesis, binding and electrophysiology assays

    PMID:34509475

    Open questions at the time
    • Single lab
    • SUMO-acceptor sites and physiological triggers incompletely defined
  30. 2021 Medium

    Identified M1R/PKC phosphorylation at T217 in nucleus accumbens regulating aversive learning, extending KCNQ2 function to reward-circuit behavior.

    Evidence In vitro PKC kinase assay, phospho-specific detection in vivo, conditional NAc knockout, behavior

    PMID:34878647

    Open questions at the time
    • Single lab
    • How T217 phosphorylation alters channel gating not defined
  31. 2022 High

    Demonstrated KCNQ2 forms KCNQ3-independent heteromers with KCNQ5 in native brain, expanding the repertoire of M-channel compositions.

    Evidence Split-intein covalent tandems, electrophysiology, native-brain mass spectrometry

    PMID:35320039

    Open questions at the time
    • Functional distinction of KCNQ2/5 vs KCNQ2/3 channels in vivo unclear
    • Stoichiometry of trimeric assemblies undefined
  32. 2022 Medium

    Identified BACE1 as a partner that recruits KCNQ2/3 to lipid rafts via BACE1 palmitoylation, adding membrane-microdomain control of channel localization.

    Evidence Spectral FRET with raft/non-raft probes and palmitoylation-deficient BACE1 in HEK cells

    PMID:35201266

    Open questions at the time
    • Heterologous system only
    • Functional impact on M-current not quantified
  33. 2022 Medium

    Linked Kcnq2 downregulation in ventral hippocampal glutamatergic neurons to ketamine's sustained antidepressant action, implicating M-channels in mood regulation.

    Evidence Cell-type transcriptomics, electrophysiology, retigabine augmentation, behavior in mice

    PMID:35649415

    Open questions at the time
    • Mechanism connecting ketamine to Kcnq2 downregulation not reconstituted
    • Causality of downregulation vs marker unclear
  34. 2023 High

    Showed that a single gain-of-function variant (R201C) produces opposite excitability effects in different neuron types, resolving why GOF mutations cause epilepsy.

    Evidence Transgenic R201C knock-in mice with patch clamp in L2/3 and CA1 neurons, compared to KCNQ3 R231C

    PMID:37607817

    Open questions at the time
    • Circuit-level consequence of opposing cell-type effects not fully resolved
    • Behavioral phenotype not detailed here

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many post-translational modifications, accessory partners, and channel compositions are integrated to set M-current in specific neuron types in vivo remains unresolved.
  • No unified in vivo model of combined CaM/PIP2/phospho/SUMO regulation
  • Functional roles of KCNQ2/5 and trimeric channels in distinct circuits undefined
  • No high-resolution structure of the human Kv7.2 channel in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 2
Partners
ANK3BACE1CALM1FGF14KCNQ3KCNQ5NEDD4L
Complex memberships
Kv7.2/Kv7.3 heterotetramerKv7.2/Kv7.5 heteromeric channelaxon initial segment ankyrin-G complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 KCNQ2 channels are functional components of axon initial segments and nodes of Ranvier, colocalizing with ankyrin-G and voltage-dependent Na+ channels throughout the CNS and PNS; ankyrin-G and KCNQ2 can be coimmunoprecipitated from brain. KCNQ channel blockers prolong repolarization of the action potential in neonatal nerves. Immunohistochemistry, coimmunoprecipitation from brain tissue, pharmacological electrophysiology (retigabine and linopirdine) The Journal of neuroscience High 14762142
2002 Calmodulin (CaM) is an auxiliary subunit that binds constitutively to KCNQ2 via two conserved C-terminal motifs (resembling an IQ motif). CaM binding is required for channel function: KCNQ2 mutants deficient in CaM binding fail to generate detectable currents when coexpressed with KCNQ3 even though they reach the membrane and assemble with KCNQ3. CaM coimmunoprecipitates with KCNQ2/3 from mouse brain. Yeast two-hybrid screen, coimmunoprecipitation from mouse brain, CHO cell electrophysiology, truncation and point mutagenesis of CaM-binding motifs The Journal of neuroscience High 12223552
2000 Co-expression of KCNQ2 and KCNQ3 increases surface expression of both subunits (KCNQ2 ~5-fold, KCNQ3 >10-fold); increased current upon co-expression is primarily due to increased surface expression. A BFNC-associated KCNQ2 truncation mutant lacking the C-terminus fails to reach the surface and fails to stimulate KCNQ3 surface expression. Single-channel conductance for KCNQ2 homomers is ~18 pS. Noise analysis, single-channel patch recording, surface biotinylation assay in Xenopus oocytes The Journal of biological chemistry High 10788442
2007 Calmodulin binding controls KCNQ2 channel trafficking: disruption of CaM binding (including the BFNC mutation R353G) leads to ER retention of KCNQ2, reducing plasma membrane expression. Overexpression of Ca2+-CaM in the R353G mutant partially restores channel distribution; sequestering calmodulin or expressing Ca2+-binding-incompetent CaM retains wild-type channels in the ER. Live-cell fluorescence imaging, subcellular fractionation, calmodulin overexpression/sequestration in transfected cells FASEB journal High 17993630
2004 M1 muscarinic receptor-mediated inhibition of KCNQ2/KCNQ3 current proceeds through a Gq-protein cycle: constitutively active Gαq/Gα11 (but not Gα13) causes PIP2 depletion from the plasma membrane and tonic inhibition of KCNQ current; RGS2 blocks PIP2 hydrolysis and current suppression; competitive inhibitors of G-protein nucleotide exchange lengthen and reduce inhibition; the sequence is receptor → Gq activation (Mg2+-dependent) → PLC → PIP2 hydrolysis → channel closure. Whole-cell patch clamp and confocal microscopy in tsA-201 cells; co-expression of constitutively active and dominant-negative G-protein subunits, RGS2; optical PIP2 probe (GFP-PH domain); kinetic modeling The Journal of general physiology High 15173220
2003 The C-terminal domain of KCNQ2 and KCNQ3 mediates their heteromeric interaction. Functional interaction requires a conserved ~80 amino acid A-domain plus either the B-domain or the proximal C-terminal region between S6 and the A-domain. There is no functional interaction between KCNQ2/3 and KCNQ1. Chimeric channel construction, Xenopus oocyte expression, two-microelectrode voltage clamp The Journal of physiology High 12640002
2015 Gain-of-function mutations in the voltage-sensing domain of Kv7.2 (R144Q, R201C, R201H) and Kv7.3 (R230C) stabilize the activated state of the channel; the R201 residue forms an intricate network of electrostatic interactions with neighboring negatively charged residues in the resting/intermediate states (confirmed by disulfide trapping). These mutations cause epilepsy through increased M-current activity reducing inhibitory interneuron output rather than intrinsic hyperexcitability. Electrophysiology in transfected mammalian cells, multistate structural modeling, disulfide trapping experiments, computational hippocampal circuit modeling The Journal of neuroscience High 25740509
2015 AnkyrinG (AnkG) anchors KCNQ2 (and KCNQ3) to the axon initial segment and nodes of Ranvier. KCNQ2 and KCNQ3 anchor peptides bind to overlapping but distinct sites near the AnkG N-terminus (ankyrin repeats 1-7). Phosphorylation by protein kinase CK2 augments KCNQ2/3 binding to AnkG. An alternatively spliced AnkG N-terminus selectively gates access to the KCNQ2/3 binding site but not the Nav1.2 binding site, providing a mechanism for the ~40:1 Nav:KCNQ conductance ratio at the distal AIS. Pulldown assays, co-immunoprecipitation, mutagenesis of AnkG repeat residues, in vitro CK2 phosphorylation assays The Journal of biological chemistry High 25998125
2007 Nedd4-2 (but not Nedd4) ubiquitinates KCNQ2/3 channels and reduces K+ current amplitude. The C-terminal region of KCNQ3 is required for Nedd4-2-mediated regulation. Nedd4-2 directly interacts with KCNQ2/3 (demonstrated by GST-fusion pulldown and co-immunoprecipitation) and can ubiquitinate KCNQ2/3 in transfected cells. Xenopus oocyte expression, electrophysiology, GST-fusion pulldown, co-immunoprecipitation, ubiquitination assay in transfected cells The Journal of biological chemistry High 17322297
2014 Protein kinase CK2, tethered to KCNQ2 channels, phosphorylates calmodulin, which strengthens calmodulin binding to KCNQ2, confers resistance to PIP2 depletion, and increases KCNQ2 current amplitude. Protein phosphatase 1 (PP1) is also tethered to KCNQ2 via a KVXF motif in the N-terminal tail; mutation of this PP1 binding site augments current density. CK2 inhibition suppresses native M-current in rat sympathetic neurons. Electrophysiology in HEK cells and rat SCG neurons, co-immunoprecipitation of CK2 and PP1 with KCNQ2, site-directed mutagenesis of PP1 binding motif, CK2 phosphorylation assay on calmodulin The Journal of biological chemistry High 24627475
2006 PP2A-Bγ subunit interacts with KCNQ2 (identified by yeast two-hybrid screening of brain cDNA library) and significantly increases KCNQ2 current. GSK3β phosphorylates the KCNQ2 channel, inhibiting it; this phosphorylation is decreased by lithium. Two novel splice variants of KCNQ2 with truncated C-termini are active but exert a dominant-negative effect on wild-type KCNQ2. Yeast two-hybrid screen, electrophysiology in heterologous cells, GSK3β phosphorylation assay The pharmacogenomics journal Medium 16733521
2000 Disruption of the mouse KCNQ2 gene (homozygous knockout) eliminates M-channel function; heterozygous mice have decreased KCNQ2 expression and show hypersensitivity to the convulsant pentylenetetrazole, demonstrating that reduced KCNQ2 expression causes neuronal hyperexcitability. Gene targeting/knockout in mice, pentylenetetrazole seizure threshold assay, quantitative expression analysis Journal of neurochemistry High 10854243
2008 KCNQ2 (with KCNQ3) contributes to the apamin-insensitive medium afterhyperpolarization current (ImAHP) in hippocampal dentate granule cells (~50% reduction in KCNQ2 or KCNQ3 knockout mice); the same KCNQ subunits also contribute to the calcium-activated slow afterhyperpolarization current (IsAHP). Hippocalcin may link calcium signaling to these KCNQ-dependent processes. Whole-cell patch clamp in hippocampal slices from KCNQ2 and KCNQ3 knockout mice; pharmacological manipulation with KCNQ blockers and openers Proceedings of the National Academy of Sciences High 19060215
2006 A naturally occurring Kcnq2 C-terminal deletion mutation (Szt1) in mice reduces M-current amplitude and density in CA1 pyramidal neurons and impairs spike frequency adaptation, demonstrating that KCNQ2 is required for native neuronal M-current and regulation of action potential firing. Perforated-patch electrophysiology in hippocampal brain slices from Szt1 mutant mice The Journal of neuroscience High 16481438
2012 The Kv7.2/Kv7.3 heterotetramer assembles predominantly as a 2:2 stoichiometry with random (non-fixed) subunit arrangement, as revealed by atomic force microscopy imaging of antibody-decorated isolated channel complexes. Subunit stoichiometry is variable when DNA ratio of the two subunits is varied. Atomic force microscopy imaging of antibody-decorated isolated channel complexes, co-purification with immunoaffinity beads The Journal of biological chemistry High 22334706
2013 Calmodulin orchestrates heteromeric assembly of KCNQ2/KCNQ3 and their targeting to the axon initial segment. Abolishing CaM interaction in KCNQ3 (I342A mutation) strongly decreases heteromeric association with KCNQ2 and impairs AIS targeting; exogenous CaM rescues trafficking. Both apoCaM and Ca2+/CaM bind to KCNQ2/3 C-terminal domains and regulate their heteromeric assembly. Co-immunoprecipitation, immunofluorescence of AIS targeting in neurons, CaM rescue experiments, mutagenesis in KCNQ3 and KCNQ2 Molecular and cellular neurosciences High 24333508
2014 Dominant-negative KCNQ2 encephalopathy mutations cause loss of function; 3 pore mutations globally reduce current amplitudes and 2 voltage-sensor mutations cause depolarizing shifts of the activation curve at subthreshold potentials, all more severe than typical haploinsufficiency-causing BFNC mutations. Retigabine partially reverses these dominant-negative effects. Two-microelectrode voltage clamp in Xenopus oocytes, surface biotinylation assay; systematic comparison of 7 encephalopathy mutations Annals of neurology High 24318194
2016 The KCNQ2 p.V175L mutation (in the voltage-sensing domain) causes a 25-40 mV hyperpolarizing shift in the conductance-voltage relationship and faster activation kinetics (gain-of-function) without affecting AIS localization, demonstrating that gain-of-function gating changes (not altered localization) can cause early-onset epileptic encephalopathy. Whole-cell patch clamp in CHO cells, immunofluorescence for AIS localization in neurons, Western blotting Epilepsia Medium 27030113
2015 The KCNQ2 p.A294V encephalopathy mutation reduces total KCNQ2 expression to ~20% of WT in CHO cells and produces no measurable current alone; in neurons, it causes mislocalization of heteromeric channels to the somatodendritic compartment rather than AIS. In contrast, the benign p.A294G mutation does not affect AIS targeting, indicating that subcellular mislocalization rather than M-current reduction alone determines disease severity. Patch clamp in CHO cells, Western blotting, immunofluorescence in neurons comparing AIS vs. somatodendritic distribution Neurobiology of disease High 26007637
2016 FGF14 positively regulates KCNQ2/3 channels: FGF14 knockdown reduces KCNQ2 at the AIS and reduces whole-cell KCNQ currents. FGF14 interacts with KCNQ2 at a site distinct from the FGF14-Nav channel interaction surface, enabling FGF14 to bridge Nav1.6 and KCNQ2, acting as an organizer of AIS channel localization. siRNA knockdown, co-immunoprecipitation, immunofluorescence of AIS localization, whole-cell patch clamp Proceedings of the National Academy of Sciences Medium 27994149
2016 KCNQ2 R198Q is a gain-of-function variant that shifts current activation gating to hyperpolarized potentials; in neurons, Kv7.2 R198Q similarly localizes to the axon initial segment as wild-type, indicating that gating changes rather than altered subcellular distribution are the pathogenic mechanism. Whole-cell patch clamp in heterologous cells, immunofluorescence of AIS localization in neurons Epilepsia Medium 27861786
2016 Kv7.2/7.3 channels at the AIS exhibit extraordinarily high steady-state stability and very low surface lateral mobility. At high glutamate loads, KCNQ2/3 undergoes rapid irreversible endocytosis requiring activation of NR2B-containing NMDA receptors, Ca2+ influx, and calpain activation (excitotoxic mechanism). This endocytosis is selective for AnkG-bound AIS proteins (Nav1.2 also endocytosed, not AIS GABAA receptors). Live-cell fluorescence imaging with novel SEP-TAC-Kv7.3 phluorin chimera in dissociated hippocampal neurons; pharmacological dissection of endocytosis mechanism The Journal of neuroscience High 26888935
2018 Epileptic encephalopathy mutations in calmodulin-binding helices A and B of Kv7.2 (R333W, K526N, R532W, M518V) reduce axonal surface expression of heteromeric channels; the M518V mutation additionally reduces CaM binding, induces ubiquitination, and accelerates proteasome-dependent Kv7.2 degradation (rescued by co-expression of Kv7.3). Mutations R333W, K526N, and R532W also alter PIP2 gating modulation revealing novel PIP2 binding residues. M518V expression increases neuronal death. Surface biotinylation, co-immunoprecipitation of CaM, ubiquitination assay, proteasome inhibitor experiments, whole-cell patch clamp, live-cell imaging in neurons Neurobiology of disease High 30008368
2009 The rate-limiting step in M1 muscarinic receptor-mediated suppression of Kv7.2/7.3 M-current is PIP2 hydrolysis (time constant ~6.7 s), not earlier steps (receptor activation <100 ms, M1R/Gβ interaction 200 ms). PLC overexpression accelerates M-current suppression ~3-fold, confirming that PLC availability limits the rate. Channel release of PIP2 and closure are rapid once PLC is active. Pairwise optical FRET measurements of each signaling step (M1R activation, Gβ interaction, Gαq/Gβ separation, Gαq/PLC interaction, PIP2 hydrolysis) combined with electrophysiology and PLC overexpression The Journal of general physiology High 19332618
2007 In sympathetic neurons, M-current inhibition by bradykinin can use either an IP3/Ca2+-dependent mechanism (product-dependent) or a PIP2 substrate-depletion-dependent mechanism depending on Ca2+ availability and PIP2 synthesis rates, as demonstrated by fluorescent PIP2 sensor (tubby-R332H-cYFP) measurements showing that bradykinin depletes only ~1/3 of the PIP2 depleted by oxotremorine-M under normal conditions, but equally depletes PIP2 when synthesis is blocked by wortmannin. Live-cell fluorescence imaging with tubby-PIP2 sensor in single sympathetic neurons, pharmacological manipulation (wortmannin, thapsigargin) The Journal of physiology Medium 17395626 17447081
2016 Phosphorylation of a cluster of five serine residues (S427/S436/S438/S446/S455) within a PIP2-binding domain of Kv7.2 by CDK5, p38 MAPK, CaMKIIα, and PKA is required to maintain the channel's sensitivity to PIP2 depletion. Alanine substitution of all five serines (A5 mutant) reduces sensitivity to PIP2 depletion via Dr-VSP and attenuates M1 muscarinic receptor-mediated channel regulation (but not bradykinin receptor regulation). LC-MS/MS phosphoproteomics of Kv7.2 immunoprecipitates from rat brain and transfected cells, Dr-VSP PIP2 depletion assay, patch clamp, in vitro kinase assay with purified Kv7.2 C-terminus The Journal of physiology High 27621207
2018 PKC-mediated phosphorylation of Kv7.2 at serine 559 is a key mechanism for neurotransmitter-induced M-current suppression. Kv7.2(S559A) knock-in mice show normal basal M-currents but reduced M-current suppression by muscarinic agonist, resistance to chemoconvulsant seizures, and prevention of status epilepticus-induced neuronal death and epileptogenesis after equivalent SE. Kv7.2(S559A) knock-in mouse model, primary neuron patch clamp, pilocarpine SE model, histological assessment of neuronal death, long-term EEG recording Epilepsia High 30146722
2021 SUMOylation of Kv7.2 and Kv7.3 inhibits their function: hyper-SUMOylation (in SENP2-deficient mice) reduces binding to PIP2 and reduces CaM1 binding, thereby inhibiting channel assembly and reducing M-currents. SENP2 (a deSUMOylase) is required to maintain normal M-currents; retigabine reduces SUMOylation by decreasing transcription of SUMO-activating enzyme SAE1. SENP2 knockout mice, co-immunoprecipitation, SUMOylation site mutagenesis, PIP2 binding assays, CaM binding assays, electrophysiology The Journal of biological chemistry Medium 34509475
2021 Muscarinic M1 receptor activation phosphorylates KCNQ2 at threonine 217 (T217) via PKC in the nucleus accumbens in vivo. PKC directly phosphorylates KCNQ2 at T217 in vitro. Donepezil administration and electric foot shock both induce T217 phosphorylation in the NAc in a PKC/M1R-dependent manner. Conditional deletion of Kcnq2 in the NAc enhances aversive learning. In vitro kinase assay with purified PKC, phospho-specific antibody detection in brain slices and in vivo, conditional Kcnq2 knockout in NAc, behavioral aversive learning assay Journal of neurochemistry Medium 34878647
2022 BACE1 recruits KCNQ2/3 channels to lipid-raft membrane microdomains via palmitoylation of BACE1's C-terminal cysteines. BACE1 and KCNQ2/3 form a signaling complex (confirmed by spectral FRET); palmitoylation of BACE1 is required for raft recruitment of KCNQ2/3 but not for the BACE1-KCNQ2/3 complex itself. Spectral FRET with lipid-raft (L10) and non-raft (S15) membrane probes in HEK cells, BACE1 palmitoylation-deficient (4C/A) mutant, methyl-β-cyclodextrin and anesthetic raft disruption The Journal of general physiology Medium 35201266
2022 KCNQ2 forms functional heteromeric channels with KCNQ5 independent of KCNQ3, as demonstrated by split-intein-mediated covalent KCNQ2/5 tandem formation and mass spectrometry showing KCNQ2-KCNQ5 association in native brain channels even in the absence of KCNQ3. KCNQ2/3/5 trimers may also form. Split-intein protein trans-splicing to form KCNQ2/5 tandems, electrophysiology in heterologous cells, mass spectrometry of native brain channels Proceedings of the National Academy of Sciences High 35320039
2014 Conditional knockout of Kcnq2 in peripheral sensory neurons (Cre-Lox) increases excitability of sensory neurons (increased firing, reduced spike frequency adaptation) and produces thermal hyperalgesia and mechanical allodynia in vivo, without affecting expression of other nodal components including Kv7.3. Conditional Cre-Lox knockout of Kcnq2 in sensory neurons, whole-cell patch clamp of DRG neurons, behavioral nociception assays (thermal hyperalgesia, mechanical allodynia) The Journal of comparative neurology High 24687876
2022 Ketamine's sustained antidepressant effects require downregulation of Kcnq2 in glutamatergic neurons of the ventral hippocampus; retigabine (KCNQ activator) augments ketamine's antidepressant-like behavioral effects in mice. These effects are ketamine-specific and do not modulate classical antidepressant (escitalopram) responses. Transcriptomic analysis of cell-type-specific signatures, electrophysiology, pharmacology (retigabine augmentation), and behavioral antidepressant assays in mice Neuron Medium 35649415
2020 KCNQ2 loss-of-function encephalopathy mutations in helix B residues K552T and R553L decrease calmodulin binding and axonal enrichment of Kv7.2 channels in hippocampal neurons; mutations L268F (pore), K552T, and R553L all disrupt PIP2-mediated current potentiation, revealing that these residues are critical for PIP2 interaction. Statistical mutation mapping, structural modeling, whole-cell patch clamp in hippocampal neurons, surface expression (Western blot), internalization assay, molecular dynamics simulation of PIP2 interaction Scientific reports Medium 32179837
2023 The KCNQ2 R201C gain-of-function variant has opposite effects on excitability in different neuron types: it causes hyperexcitability in cortical layer 2/3 pyramidal neurons but hypoexcitability in CA1 hippocampal pyramidal neurons. The homologous KCNQ3 R231C variant similarly shows cell-type-specific opposite effects. Transgenic knock-in mice expressing R201C variant, whole-cell patch clamp in acute brain slices from L2/3 and CA1 neurons, comparison with KCNQ3 R231C knock-in The Journal of neuroscience High 37607817

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Annals of neurology 406 22275249
2004 KCNQ2 is a nodal K+ channel. The Journal of neuroscience : the official journal of the Society for Neuroscience 354 14762142
2003 KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain : a journal of neurology 230 14534157
2015 Early and effective treatment of KCNQ2 encephalopathy. Epilepsia 204 25880994
2014 Dominant-negative effects of KCNQ2 mutations are associated with epileptic encephalopathy. Annals of neurology 188 24318194
2013 Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients. Neurology 187 24107868
2016 KCNQ2 encephalopathy: Features, mutational hot spots, and ezogabine treatment of 11 patients. Neurology. Genetics 172 27602407
2015 Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits. The Journal of neuroscience : the official journal of the Society for Neuroscience 156 25740509
2000 Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability. Journal of neurochemistry 153 10854243
2002 Calmodulin is an auxiliary subunit of KCNQ2/3 potassium channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 148 12223552
2000 Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy. The Journal of biological chemistry 141 10788442
1998 The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3. FEBS letters 124 9827540
2004 Regulation of KCNQ2/KCNQ3 current by G protein cycling: the kinetics of receptor-mediated signaling by Gq. The Journal of general physiology 111 15173220
2008 Contribution of KCNQ2 and KCNQ3 to the medium and slow afterhyperpolarization currents. Proceedings of the National Academy of Sciences of the United States of America 110 19060215
2007 Calmodulin regulates the trafficking of KCNQ2 potassium channels. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 98 17993630
2009 Fluorescence changes reveal kinetic steps of muscarinic receptor-mediated modulation of phosphoinositides and Kv7.2/7.3 K+ channels. The Journal of general physiology 93 19332618
2001 Properties of single M-type KCNQ2/KCNQ3 potassium channels expressed in mammalian cells. The Journal of physiology 92 11432988
2015 Potent KCNQ2/3-specific channel activator suppresses in vivo epileptic activity and prevents the development of tinnitus. The Journal of neuroscience : the official journal of the Society for Neuroscience 88 26063916
2016 Infantile spasms and encephalopathy without preceding neonatal seizures caused by KCNQ2 R198Q, a gain-of-function variant. Epilepsia 83 27861786
2007 Regulation of M(Kv7.2/7.3) channels in neurons by PIP(2) and products of PIP(2) hydrolysis: significance for receptor-mediated inhibition. The Journal of physiology 83 17395626
2019 Characteristics of KCNQ2 variants causing either benign neonatal epilepsy or developmental and epileptic encephalopathy. Epilepsia 77 31418850
2007 Regulation of the voltage-gated K(+) channels KCNQ2/3 and KCNQ3/5 by ubiquitination. Novel role for Nedd4-2. The Journal of biological chemistry 76 17322297
2008 KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes. Neurology 75 18625963
2016 Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations. PloS one 71 26910900
2006 A spontaneous mutation involving Kcnq2 (Kv7.2) reduces M-current density and spike frequency adaptation in mouse CA1 neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 68 16481438
2022 Ketamine exerts its sustained antidepressant effects via cell-type-specific regulation of Kcnq2. Neuron 66 35649415
2015 An Ankyrin-G N-terminal Gate and Protein Kinase CK2 Dually Regulate Binding of Voltage-gated Sodium and KCNQ2/3 Potassium Channels. The Journal of biological chemistry 66 25998125
1999 Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions. Human genetics 65 10323247
2015 A recurrent KCNQ2 pore mutation causing early onset epileptic encephalopathy has a moderate effect on M current but alters subcellular localization of Kv7 channels. Neurobiology of disease 64 26007637
2003 C-terminal interaction of KCNQ2 and KCNQ3 K+ channels. The Journal of physiology 61 12640002
2006 PP2A-Bgamma subunit and KCNQ2 K+ channels in bipolar disorder. The pharmacogenomics journal 58 16733521
2007 Developmental changes in KCNQ2 and KCNQ3 expression in human brain: possible contribution to the age-dependent etiology of benign familial neonatal convulsions. Brain & development 57 18166285
2007 Deletions or duplications in KCNQ2 can cause benign familial neonatal seizures. Journal of medical genetics 56 17675531
2020 The Role of Kv7.2 in Neurodevelopment: Insights and Gaps in Our Understanding. Frontiers in physiology 54 33192566
2016 FGF14 is a regulator of KCNQ2/3 channels. Proceedings of the National Academy of Sciences of the United States of America 49 27994149
2011 Distribution of M-channel subunits KCNQ2 and KCNQ3 in rat hippocampus. NeuroImage 48 21787867
2006 Immunohistochemical analysis of KCNQ2 potassium channels in adult and developing mouse brain. Brain research 48 16500630
2020 Identifying mutation hotspots reveals pathogenetic mechanisms of KCNQ2 epileptic encephalopathy. Scientific reports 46 32179837
2013 Calmodulin orchestrates the heteromeric assembly and the trafficking of KCNQ2/3 (Kv7.2/3) channels in neurons. Molecular and cellular neurosciences 43 24333508
2018 Pharmacological Targeting of Neuronal Kv7.2/3 Channels: A Focus on Chemotypes and Receptor Sites. Current medicinal chemistry 41 29022505
2007 PIP(2)-dependent inhibition of M-type (Kv7.2/7.3) potassium channels: direct on-line assessment of PIP(2) depletion by Gq-coupled receptors in single living neurons. Pflugers Archiv : European journal of physiology 41 17447081
2016 Live Imaging of Kv7.2/7.3 Cell Surface Dynamics at the Axon Initial Segment: High Steady-State Stability and Calpain-Dependent Excitotoxic Downregulation Revealed. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 26888935
2016 A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity. Epilepsia 40 27030113
2015 Variable clinical expression in patients with mosaicism for KCNQ2 mutations. American journal of medical genetics. Part A 40 25959266
2006 Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neuroscience letters 40 17184917
2014 Channel-anchored protein kinase CK2 and protein phosphatase 1 reciprocally regulate KCNQ2-containing M-channels via phosphorylation of calmodulin. The Journal of biological chemistry 39 24627475
2021 KCNQ2-DEE: developmental or epileptic encephalopathy? Annals of clinical and translational neurology 36 33616268
2015 Epilepsy-causing mutations in Kv7.2 C-terminus affect binding and functional modulation by calmodulin. Biochimica et biophysica acta 36 26073431
2014 Kv7.2 regulates the function of peripheral sensory neurons. The Journal of comparative neurology 35 24687876
2022 KCNQ2 R144 variants cause neurodevelopmental disability with language impairment and autistic features without neonatal seizures through a gain-of-function mechanism. EBioMedicine 34 35780567
2021 Dyshomeostatic modulation of Ca2+-activated K+ channels in a human neuronal model of KCNQ2 encephalopathy. eLife 34 33544076
2005 Expression of a calmodulin-binding KCNQ2 potassium channel fragment modulates neuronal M-current and membrane excitability. Proceedings of the National Academy of Sciences of the United States of America 33 16263935
2020 A knock-in mouse model for KCNQ2-related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment. Epilepsia 32 32239694
2006 Infantile seizures and other epileptic phenotypes in a Chinese family with a missense mutation of KCNQ2. European journal of pediatrics 32 16691402
2020 Genotype-phenotype correlations in patients with de novo KCNQ2 pathogenic variants. Neurology. Genetics 31 33659638
2019 Heterozygous loss of epilepsy gene KCNQ2 alters social, repetitive and exploratory behaviors. Genes, brain, and behavior 30 31283873
2018 Gq-Coupled Muscarinic Receptor Enhancement of KCNQ2/3 Channels and Activation of TRPC Channels in Multimodal Control of Excitability in Dentate Gyrus Granule Cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 30593498
2022 KCNQ2 and KCNQ5 form heteromeric channels independent of KCNQ3. Proceedings of the National Academy of Sciences of the United States of America 29 35320039
2018 Reduced axonal surface expression and phosphoinositide sensitivity in Kv7 channels disrupts their function to inhibit neuronal excitability in Kcnq2 epileptic encephalopathy. Neurobiology of disease 29 30008368
2021 Kcnq2/Kv7.2 controls the threshold and bi-hemispheric symmetry of cortical spreading depolarization. Brain : a journal of neurology 28 33768249
2009 Functional analysis of novel KCNQ2 mutations found in patients with Benign Familial Neonatal Convulsions. Neuroscience letters 27 19559753
2009 Deletions involving both KCNQ2 and CHRNA4 present with benign familial neonatal seizures. Neurology 27 19822871
2018 Attenuating M-current suppression in vivo by a mutant Kcnq2 gene knock-in reduces seizure burden and prevents status epilepticus-induced neuronal death and epileptogenesis. Epilepsia 26 30146722
2016 Phosphorylation regulates the sensitivity of voltage-gated Kv7.2 channels towards phosphatidylinositol-4,5-bisphosphate. The Journal of physiology 26 27621207
2010 Novel role of KCNQ2/3 channels in regulating neuronal cell viability. Cell death and differentiation 26 20885443
2023 KCNQ2/3 Gain-of-Function Variants and Cell Excitability: Differential Effects in CA1 versus L2/3 Pyramidal Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 37607817
2021 Flexible Stoichiometry: Implications for KCNQ2- and KCNQ3-Associated Neurodevelopmental Disorders. Developmental neuroscience 25 33794528
2012 Cooperativity between calmodulin-binding sites in Kv7.2 channels. Journal of cell science 25 23203804
2018 Neurotransmitter Pathway Genes in Cognitive Decline During Aging: Evidence for GNG4 and KCNQ2 Genes. American journal of Alzheimer's disease and other dementias 24 29338302
2018 Calmodulin: A Multitasking Protein in Kv7.2 Potassium Channel Functions. Biomolecules 24 30022004
2018 Homomeric Kv7.2 current suppression is a common feature in KCNQ2 epileptic encephalopathy. Epilepsia 24 30478917
2012 The Kv7.2/Kv7.3 heterotetramer assembles with a random subunit arrangement. The Journal of biological chemistry 24 22334706
2008 Regulation of the voltage-gated K(+) channels KCNQ2/3 and KCNQ3/5 by serum- and glucocorticoid-regulated kinase-1. American journal of physiology. Cell physiology 24 18463232
2013 Effects of KCNQ2 gene truncation on M-type Kv7 potassium currents. PloS one 23 23977150
2008 Expression and localization of K channels KCNQ2 and KCNQ3 in the mammalian cochlea. Audiology & neuro-otology 23 18827480
2005 Functional analysis of novel KCNQ2 and KCNQ3 gene variants found in a large pedigree with benign familial neonatal convulsions (BFNC). Neurogenetics 22 16235065
2016 Clinical and genetic features of 13 Spanish patients with KCNQ2 mutations. Journal of human genetics 20 27535030
2004 Ionic permeation and conduction properties of neuronal KCNQ2/KCNQ3 potassium channels. Biophysical journal 20 14990473
2022 Genetic interaction between Scn8a and potassium channel genes Kcna1 and Kcnq2. Epilepsia 19 35892317
2017 Differential Regulation of PI(4,5)P2 Sensitivity of Kv7.2 and Kv7.3 Channels by Calmodulin. Frontiers in molecular neuroscience 19 28507506
2022 Time-limited alterations in cortical activity of a knock-in mouse model of KCNQ2-related developmental and epileptic encephalopathy. The Journal of physiology 18 35389519
2019 KCNQ2 mutations in childhood nonlesional epilepsy: Variable phenotypes and a novel mutation in a case series. Molecular genetics & genomic medicine 18 31199083
2014 Severe Neonatal Epileptic Encephalopathy and KCNQ2 Mutation: Neuropathological Substrate? Frontiers in pediatrics 18 25566516
2013 The new KCNQ2 activator 4-Chlor-N-(6-chlor-pyridin-3-yl)-benzamid displays anticonvulsant potential. British journal of pharmacology 17 23176257
2011 Activation of KCNQ2/3 potassium channels by novel pyrazolo[1,5-a]pyrimidin-7(4H)-one derivatives. Pharmacology 17 21577044
2015 The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility. The Journal of pharmacology and experimental therapeutics 16 26087697
2012 Surface expression and subunit specific control of steady protein levels by the Kv7.2 helix A-B linker. PloS one 16 23115641
2022 Neuronal KCNQ2/3 channels are recruited to lipid raft microdomains by palmitoylation of BACE1. The Journal of general physiology 15 35201266
2015 A New Regulatory Mechanism for Kv7.2 Protein During Neuropathy: Enhanced Transport from the Soma to Axonal Terminals of Injured Sensory Neurons. Frontiers in cellular neuroscience 15 26696829
2020 Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy. Pharmacological research 13 32942014
2016 M-currents (Kv7.2-7.3/KCNQ2-KCNQ3) Are Responsible for Dysfunctional Autonomic Control in Hypertensive Rats. Frontiers in physiology 13 27965589
2016 Calmodulin regulates KCNQ2 function in epilepsy. American journal of translational research 13 28078031
2023 Functional characterization and in vitro pharmacological rescue of KCNQ2 pore mutations associated with epileptic encephalopathy. Acta pharmacologica Sinica 12 36932231
2022 Mouse models of Kcnq2 dysfunction. Epilepsia 12 36047730
2021 The SUMO-specific protease SENP2 plays an essential role in the regulation of Kv7.2 and Kv7.3 potassium channels. The Journal of biological chemistry 12 34509475
2021 Muscarinic signaling regulates voltage-gated potassium channel KCNQ2 phosphorylation in the nucleus accumbens via protein kinase C for aversive learning. Journal of neurochemistry 12 34878647
2020 Heteromeric Kv7.2 current changes caused by loss-of-function of KCNQ2 mutations are correlated with long-term neurodevelopmental outcomes. Scientific reports 12 32770121
2020 Two KCNQ2 Encephalopathy Variants in the Calmodulin-Binding Helix A Exhibit Dominant-Negative Effects and Altered PIP2 Interaction. Frontiers in physiology 12 33041849
2019 Identification of potassium channel proteins Kv7.2/7.3 as common partners of the dopamine and glutamate transporters DAT and GLT-1. Neuropharmacology 12 30885609
2019 Role of Kv7.2/Kv7.3 and M1 muscarinic receptors in the regulation of neuronal excitability in hiPSC-derived neurons. European journal of pharmacology 12 31238068

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