Affinage

KCND2

A-type voltage-gated potassium channel KCND2 · UniProt Q9NZV8

Length
630 aa
Mass
70.5 kDa
Annotated
2026-06-10
100 papers in source corpus 52 papers cited in narrative 52 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

KCND2 encodes Kv4.2, the principal pore-forming α-subunit of fast-inactivating A-type (ISA) K+ channels in neurons and the fast transient outward current (Ito,f) in cardiac myocytes, where genetic deletion eliminates these currents and establishes Kv4.2 as their primary molecular determinant (PMID:17122039, PMID:16293790). The cloned channel activates rapidly, inactivates with millisecond kinetics, and is 4-AP-sensitive but TEA- and dendrotoxin-insensitive (PMID:1722463); it undergoes distinct open-state and closed-state inactivation, the latter reflecting voltage-sensor desensitization (gating-charge immobilization) coupled through the S4-S5 linker and S6 to the cytoplasmic gate (PMID:11507158, PMID:18299396, PMID:19171772). Native channels are macromolecular assemblies: Kv4.2 forms octameric 4:4 complexes with cytoplasmic KChIP subunits and with transmembrane DPP6/DPP10 subunits (PMID:14623880, PMID:18364354). KChIPs bind the Kv4.2 N-terminus to mask an ER-retention signal and promote surface trafficking and reciprocal subunit stabilization (PMID:12829703, PMID:17122038, PMID:16096338), while DPP6/DPP10 accelerate inactivation, remodel voltage-sensor gating, and increase unitary conductance; ternary Kv4.2-KChIP-DPP complexes reconstitute native ISA kinetics (PMID:15454437, PMID:16123112, PMID:19279261, PMID:17130523). Channel surface density and gating are tuned by direct phosphorylation by ERK (T602/T607/S616), PKA (T38/S552), CaMKII (S438/S459), and PKC (S447/S537), with several effects requiring KChIP co-assembly and with cross-talk between kinases (PMID:11080179, PMID:10681507, PMID:15071113, PMID:16251476, PMID:18795890). Trafficking is further controlled by activity-dependent, NMDA-receptor- and Ca2+-driven clathrin-mediated internalization requiring PKA phosphorylation at S552, by Kif17-dependent dendritic transport, by NR2B-NMDAR/calpain-mediated degradation, and by Pin1 prolyl isomerization at pThr607 that dissociates the Kv4.2-DPP6 complex to regulate excitability and learning (PMID:16257958, PMID:17582333, PMID:18650329, PMID:19857555, PMID:32218435). Loss of Kv4.2 A-current enhances backpropagating action potentials and lowers the LTP threshold (PMID:17122039), and gain-of-function KCND2 mutations cause autism with epilepsy (V404Met, via altered closed-state inactivation) and paroxysmal atrial fibrillation (S447R, via impaired PKC regulation and augmented surface Ito) (PMID:24501278, PMID:29581270, PMID:30571183).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1991 High

    Established that KCND2 encodes a functional voltage-gated A-type K+ channel with a defined kinetic and pharmacological fingerprint, providing the molecular identity for native rapidly inactivating currents.

    Evidence Two-electrode voltage-clamp of cloned RK5/Kv4.2 in Xenopus oocytes

    PMID:1722463

    Open questions at the time
    • Did not establish which native currents Kv4.2 carries in vivo
    • No auxiliary subunit context
  2. 1996 High

    Defined the intracellular, closed-state mechanism of 4-AP block and its mutual exclusivity with inactivation, linking the drug site to the inactivation machinery.

    Evidence State-dependent pharmacological voltage-clamp analysis in oocytes

    PMID:8930194

    Open questions at the time
    • Exact molecular residues of the 4-AP site not mapped
  3. 1997 High

    Demonstrated that Kv4 subunits are the predominant carriers of neuronal A-current and cardiac Ito, moving Kv4.2 from a cloned channel to a physiological current determinant.

    Evidence Adenoviral dominant-negative Kv4.2 in cerebellar granule cells and ventricular myocytes

    PMID:9395498

    Open questions at the time
    • Dominant-negative suppresses all Kv4 members, not Kv4.2-specific
    • Subunit composition of native channels unresolved at this stage
  4. 2000 High

    Identified the cytoskeletal and trafficking partners and the first kinase inputs to Kv4.2, establishing the channel as a regulated, scaffolded protein rather than a static pore.

    Evidence Yeast two-hybrid/co-IP for filamin; in vitro kinase assays with phosphosite mapping for ERK and PKA

    PMID:10681507 PMID:11080179 PMID:11102480

    Open questions at the time
    • Functional consequence of individual phosphosites not yet resolved
    • In vivo phosphorylation stoichiometry unknown
  5. 2002 High

    Showed that PSD-95 clusters and stabilizes Kv4.2 at the surface and that kinase regulation requires auxiliary subunits, establishing that Kv4.2 is regulated as part of a supramolecular complex.

    Evidence Co-IP, VSAL-motif mutagenesis, surface biotinylation, and PKA epistasis with KChIP3 in oocytes

    PMID:11923279 PMID:12451113

    Open questions at the time
    • Stoichiometry of the complex not yet defined
    • Whether PSD-95 acts in native neurons not directly tested
  6. 2003 High

    Defined KChIP function and established 4:4 channel stoichiometry, explaining how cytoplasmic subunits release ER retention and build the native octameric Ito channel.

    Evidence Surface biotinylation/fractionation/co-IP for KChIP trafficking; purification and amino acid analysis for Kv4.2:KChIP2 4:4 stoichiometry

    PMID:12829703 PMID:14623880

    Open questions at the time
    • Did not address DPP subunit incorporation
    • KChIP4a inhibitory mechanism not fully resolved
  7. 2004 High

    Established CaMKII as a phosphorylation input that increases Kv4.2 protein and surface expression, and identified DPP10 as a transmembrane partner that dramatically increases surface current and accelerates gating.

    Evidence In vitro kinase assay with site mutagenesis (CaMKII); co-IP and voltage-clamp with N-terminal deletions (DPP10)

    PMID:15071113 PMID:15454437

    Open questions at the time
    • Native ternary complex composition not yet shown
    • CaMKII mechanism of stabilization unknown
  8. 2005 High

    Reconstituted native A-type channel kinetics from a defined ternary Kv4.2-KChIP3-DPP10 complex, identified Kif17 as the dendritic transport motor, and mapped KChIP interaction sites and phosphomimetic gating effects.

    Evidence Co-IP from brain plus voltage-clamp reconstitution; dominant-negative kinesin with co-IP; lysine-scanning mutagenesis; phosphomimetic mutants with KChIP3 epistasis

    PMID:16096338 PMID:16123112 PMID:16251476 PMID:16257958

    Open questions at the time
    • How transport, assembly, and phosphorylation are coordinated in vivo unresolved
  9. 2006 High

    Used genetic knockout to prove Kv4.2 is the primary determinant of dendritic A-current and cardiac Ito,f, linking it causally to synaptic plasticity threshold and reciprocal KChIP stability.

    Evidence Kv4.2 knockout mice with dendritic patch clamp, Ca2+ imaging, LTP protocols, myocyte voltage-clamp, and IHC

    PMID:16293790 PMID:17102134 PMID:17122038 PMID:17122039

    Open questions at the time
    • Compensatory remodeling complicates interpretation of cardiac phenotype
    • Whether reduced LTP threshold causes behavioral change not addressed here
  10. 2007 High

    Established activity-dependent trafficking control of Kv4.2 and additional scaffolding/signaling routes coupling synaptic activity to channel surface density and excitability.

    Evidence Live imaging plus pharmacology (clathrin/NMDAR/Ca2+) for internalization; SAP97 co-IP/RNAi; mGlu5-ERK-S616 with S616A mutant and knockout behavior

    PMID:17582333 PMID:17635915 PMID:18045912

    Open questions at the time
    • Endocytic adaptor proteins linking phosphorylation to clathrin not identified
    • Coupling between internalization and degradation pathways unclear
  11. 2008 High

    Pinpointed PKA phosphorylation at S552 as the trigger for activity-dependent internalization and clarified that closed-state inactivation is voltage-sensor desensitization independent of the N-terminus.

    Evidence Live imaging with S552A mutant and PKA pharmacology; gating-current measurements from CTX-blocked engineered channels

    PMID:18299396 PMID:18650329

    Open questions at the time
    • Downstream endocytic machinery recognizing pS552 unknown
  12. 2009 High

    Dissected the biophysical basis of DPP-subunit modulation (conductance, voltage-sensor remodeling), the structural determinants of closed-state inactivation, the PKC phosphorylation input with PKC-ERK cross-talk, and CaV3.1 coupling.

    Evidence Single-channel recordings with dpp6 knockout; gating currents with DPPX-S; alanine-scanning/double-mutant cycles; in vitro PKC kinase and sequential kinase assays; co-expression electrophysiology with CaV3.1

    PMID:17130523 PMID:18795890 PMID:19171772 PMID:19279261 PMID:19441798 PMID:20458163

    Open questions at the time
    • CaV3.1 coupling shown only in heterologous cells
    • Structural mechanism of DPP conductance increase inferred from electrostatics, not structure
  13. 2010 High

    Resolved isoform-specific KChIP trafficking requirements (KChIP4a requires S552 phosphorylation; AKAPs as partners) and identified extrasynaptic NR2B-NMDAR/calpain proteolysis as a degradative downregulation pathway.

    Evidence Co-IP, surface biotinylation, pulse-chase with S552A mutant; pharmacological NR2B and calpain dissection with protein analysis

    PMID:19857555 PMID:20045463

    Open questions at the time
    • Calpain cleavage sites on Kv4.2 not mapped
    • AKAP identity not specified
  14. 2011 High

    Quantified the actual Kv4.2 dendritic distribution by immunogold EM, revealing a shallower proximo-distal gradient than electrophysiology predicted.

    Evidence SDS-FRL quantitative immunogold EM validated with Kv4.2 knockout negative control

    PMID:22098631

    Open questions at the time
    • Discrepancy between channel density and functional A-current gradient unexplained
    • Does not address channel open probability or auxiliary subunit distribution
  15. 2014 High

    Provided the first human disease link, showing a de novo KCND2 gain-of-function mutation causes autism with epilepsy through slowed inactivation.

    Evidence Whole-exome sequencing of affected twins plus HEK-cell voltage-clamp of V404M with wild-type co-expression

    PMID:24501278

    Open questions at the time
    • In vivo neuronal consequences of V404M not tested
    • Genotype-phenotype generalizability limited to single family
  16. 2015 Medium

    Defined GPCR-to-channel signaling convergence (PACAP/PAC1 via PKA+ERK) and a specific cardiac redox regulatory mechanism through a Cys320/Cys529 disulfide.

    Evidence Patch clamp with PKA/ERK inhibitors and biotinylation; C320A/C529A mutagenesis with H2S application in cardiomyocytes

    PMID:25756524 PMID:26456351

    Open questions at the time
    • PACAP cascade characterized in single lab
    • Physiological source of the disulfide oxidation in vivo unclear
  17. 2016 High

    Placed post-transcriptional Kv4.2 silencing by miR-324-5p in the seizure-onset pathway, validated by genetic epistasis.

    Evidence RISC IP, antagomir, kainic acid seizure model, and Kcnd2 knockout epistasis

    PMID:27681419

    Open questions at the time
    • Other targets of miR-324-5p may contribute to seizure phenotype
  18. 2018 High

    Mechanistically resolved the V404M epilepsy/autism mutation as enhancing closed-state inactivation while impairing open-channel inactivation, and identified an S447R gain-of-function mutation causing atrial fibrillation via disrupted PKC regulation.

    Evidence Detailed kinetic voltage-clamp of V404M closed- vs open-state inactivation; WES/linkage plus oocyte electrophysiology of S447R in homo- and heterotetramers

    PMID:29581270 PMID:30571183

    Open questions at the time
    • No high-resolution structure confirming the proposed steric mechanism
    • S447R cardiac phenotype not modeled in vivo
  19. 2020 High

    Identified Pin1 prolyl isomerization at pThr607 as a switch dissociating the Kv4.2-DPP6 complex, and GSK3β phosphorylation at S616 as a stress-related regulator of plasticity and behavior, linking channel regulation to cognition and mood.

    Evidence T607A knock-in mice with co-IP, patch clamp, and behavior (Pin1); AAV-shRNA GSK3β knockdown with patch clamp and behavior

    PMID:32209671 PMID:32218435

    Open questions at the time
    • Whether Pin1 and GSK3β pathways intersect at overlapping C-terminal sites not tested
    • Therapeutic targeting not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the assembled Kv4.2-KChIP-DPP ternary complex and an integrated model reconciling channel density, phosphorylation state, and the functional A-current gradient remain to be established.
  • No experimental structure of the native octameric ternary complex in the corpus
  • Quantitative reconciliation of immunogold density with functional current gradient unresolved
  • Coordinated logic of multi-kinase phosphorylation in vivo not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1643685 Disease 4 R-HSA-9609507 Protein localization 4 R-HSA-397014 Muscle contraction 2
Partners
DLG1DLG4DPP10DPP6FLNAKCNIP2KCNIP3KIF17
Complex memberships
Kv4.2-DPP6 (4:4 ISA channel)Kv4.2-KChIP (4:4 octameric A-type/Ito channel)Kv4.2-KChIP3-DPP10 ternary channel complex

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Kv4.2 (RK5) encodes a voltage-sensitive A-type K+ channel that activates rapidly, inactivates with time constants of 15 and 60 ms, is sensitive to 4-AP (IC50 ~5 mM), and is insensitive to TEA and dendrotoxins, as demonstrated by heterologous expression in Xenopus oocytes. Two-electrode voltage-clamp in Xenopus oocytes FEBS letters High 1722463
1996 4-AP blocks Kv4.2 channels exclusively from the intracellular side in the closed state; binding and channel inactivation are mutually exclusive, indicating the 4-AP binding site is at or adjacent to the cytoplasmic domains involved in inactivation. Two-electrode voltage-clamp in Xenopus oocytes with pharmacological analysis The Journal of pharmacology and experimental therapeutics High 8930194
1997 Dominant-negative truncated Kv4.2 (Kv4.2ST, truncated after the first transmembrane segment) suppresses A-type currents in cerebellar granule cells and transient outward current (Ito) in rat ventricular myocytes when delivered by adenoviral gene transfer, demonstrating that Kv4 family subunits are the predominant contributors to these currents. Adenoviral dominant-negative overexpression, whole-cell patch clamp, cotransfection in CHO-K1 cells The Journal of biological chemistry High 9395498
1997 Kv4.2 protein is clustered at the postsynaptic membrane of supraoptic nucleus neurons, specifically concentrated at synaptic contacts on somata and dendrites, as shown by immunoelectron microscopy. Confocal and immunoelectron microscopy Neuroscience Medium 9070739
1999 Kvβ1.2 co-expression with Kv4.2 in HEK293 cells confers sensitivity to redox modulation and hypoxia to Kv4.2 channels; this O2 sensitivity is membrane-delimited and involves a hemoproteic O2 sensor, and is not observed with Shaker channels co-expressed with Kvβ1.2. Transfection in HEK293 cells, whole-cell patch clamp, cell-free patches, pharmacological redox agents The Journal of general physiology High 10352037
2000 ERK2 directly phosphorylates Kv4.2 at three C-terminal sites: Thr602, Thr607, and Ser616, as determined by in vitro kinase assays on GST-fusion proteins and phosphopeptide mapping, and ERK-phosphorylated Kv4.2 is detected in rat hippocampus in vivo. In vitro kinase assay with GST-fusion proteins, phosphopeptide mapping, amino acid sequencing, phospho-selective antibodies, COS-7 cell transfection Journal of neurochemistry High 11080179
2000 PKA directly phosphorylates Kv4.2 at Thr38 (N-terminus) and Ser552 (C-terminus), identified by in vitro phosphorylation of GST-fusion proteins, phosphopeptide mapping, and confirmed in COS-7 cells and in rat hippocampal area CA1. In vitro PKA kinase assay with GST-fusion proteins, phosphopeptide mapping, amino acid sequencing, phospho-selective antibodies, COS-7 cell transfection The Journal of biological chemistry High 10681507
2000 Kv4.2 directly interacts with the actin-binding protein filamin via yeast two-hybrid and co-immunoprecipitation from brain and in vitro; this interaction localizes Kv4.2 to filopodial roots in filamin+ cells and increases whole-cell Kv4.2 current density ~2.7-fold compared to filamin− cells. Yeast two-hybrid, co-immunoprecipitation from brain and in vitro, immunocytochemistry, whole-cell patch clamp in filamin+/− cells The Journal of neuroscience High 11102480
2000 Kv4.2 protein in rat ventricular myocytes localizes predominantly to the transverse-axial tubular system, as demonstrated by immunofluorescence and correlative immunoelectron microscopy (FluoroNanogold). Immunofluorescence, immunoelectron microscopy (FluoroNanogold), confocal microscopy Journal of molecular and cellular cardiology Medium 10860776
2001 Kv4.2 channels undergo both open-state and closed-state inactivation; deletion of the N-terminus (Δ2-40) slows fast and intermediate components of open-state inactivation but does not affect closed-state inactivation or recovery, establishing that N-terminal inactivation is distinct from closed-state inactivation. Site-directed mutagenesis, whole-cell patch clamp in HEK293 cells, kinetic modeling The Journal of physiology High 11507158
2001 MiRP1 (KCNE2) associates with Kv4.2 to form a stable complex (co-immunoprecipitation), slows activation and inactivation rates of Kv4.2 and shifts voltage dependence of gating positively, without affecting current amplitude; MiRP1 has no effect on Kv1.4. Xenopus oocyte expression, two-electrode voltage clamp, co-immunoprecipitation Circulation research High 11375270
2002 PSD-95 interacts with Kv4.2 via the C-terminal VSAL motif of Kv4.2 and the PDZ domains of PSD-95; PSD-95 co-expression increases surface expression and clustering of Kv4.2, an effect requiring PSD-95 palmitoylation and the intact VSAL motif. Co-immunoprecipitation, site-directed mutagenesis, biotinylation surface assay, deconvolution microscopy in mammalian cell lines The Journal of biological chemistry High 11923279
2002 PKA phosphorylation of the Kv4.2 α-subunit is necessary but not sufficient for channel modulation; the ancillary subunit KChIP3 must also be present for PKA to alter channel properties, demonstrating that PKA regulates Kv4.2 as part of a supramolecular complex. Xenopus oocyte expression, two-electrode voltage clamp, co-expression of wild-type and mutant Kv4.2 with/without KChIP3 The Journal of neuroscience High 12451113
2003 KChIPs1-3 co-expression with Kv4.2 releases endoplasmic reticulum retention of Kv4.2 and promotes trafficking to the cell surface by masking an N-terminal hydrophobic domain of Kv4.2; KChIP co-expression also increases Kv4.2 steady-state expression, alters phosphorylation, detergent solubility, and stability. KChIP4a does not exert these effects and negatively influences other KChIPs. Co-immunoprecipitation, immunofluorescence, Western blot, surface biotinylation, subcellular fractionation in heterologous cells and native tissue The Journal of biological chemistry High 12829703
2003 Kv4.2 and KChIP2 form octameric complexes with four subunits each, as determined by purification of native Ito channels and direct amino acid analysis of subunit molar ratios. Protein purification, electron microscopy, direct amino acid analysis, biochemical stoichiometry The Journal of biological chemistry High 14623880
2003 PSD-95, when palmitoylated, recruits Kv1.4 but not Kv4.2 into lipid rafts; a portion of Kv4.2 is nonetheless raft-associated in rat brain membranes, and Kv4.2 is found in Thy-1-containing rafts in hippocampal neurons. Lipid raft fractionation, co-immunoprecipitation, immunostaining, raft patching in heterologous cells and rat brain membranes The Journal of biological chemistry Medium 14559911
2004 CaMKII directly phosphorylates Kv4.2 at Ser438 and Ser459 in vitro; CaMKII phosphorylation does not alter channel gating properties but increases Kv4.2 protein levels and surface expression, thereby increasing peak A-type current amplitude and reducing neuronal excitability. In vitro kinase assay, site-directed mutagenesis, Xenopus oocyte expression, whole-cell patch clamp in hippocampal neurons with constitutively active CaMKII The Journal of neuroscience High 15071113
2004 DPP10 co-immunoprecipitates with Kv4.2 from oocytes; DPP10 co-expression increases Kv4.2 surface current ~5-fold, accelerates inactivation and recovery, and shifts voltage dependence of activation (~−19 mV) and inactivation (~−7 mV); the cytoplasmic N-terminal domain of DPP10 determines the acceleration of inactivation. Co-immunoprecipitation, two-electrode voltage clamp in Xenopus oocytes, N-terminal deletion constructs Biophysical journal High 15454437
2005 ERK/MAPK phosphorylation of Kv4.2 at T607 (mimicked by T607D mutation) causes a rightward shift in the activation curve and reduces current amplitude; this effect requires KChIP3 co-expression. The S616D mutation causes an opposite leftward shift in activation voltage. Site-directed mutagenesis (phosphomimetic), Xenopus oocyte expression, two-electrode voltage clamp, co-expression with KChIP3 American journal of physiology. Cell physiology High 16251476
2005 Kv4.2 is transported to dendrites by the kinesin Kif17; dominant-negative Kif17 inhibits dendritic localization of both introduced and endogenous Kv4.2 but not other kinesin dominant negatives; Kv4.2 and Kif17 co-immunoprecipitate from brain lysate; the interaction involves the extreme C-terminus of Kv4.2, not the dileucine motif. Dominant-negative kinesin constructs, co-immunoprecipitation from brain and COS cells, confocal imaging in cortical neurons The Journal of biological chemistry High 16257958
2005 Kv4.2, KChIP3, and DPP10 form ternary complexes in rat brain and in Xenopus oocytes (co-immunoprecipitation); ternary channel complexes exhibit recovery from inactivation (τrec ~18-26 ms) matching native ISA and significantly faster than binary complexes, reconstituting native neuronal A-type channel properties. Immunoprecipitation from rat brain and Xenopus oocytes, two-electrode voltage clamp in oocytes and CHO cells The Journal of physiology High 16123112
2006 Targeted deletion of Kv4.2 in mice eliminates dendritic A-type K+ currents in hippocampal CA1 pyramidal neurons, increases backpropagating action potential amplitude and Ca2+ influx, and lowers the threshold for LTP induction with theta burst pairing, establishing Kv4.2 as the primary determinant of dendritic A-current and a regulator of synaptic plasticity. Kv4.2 knockout mice, whole-cell and dendritic patch clamp, Ca2+ imaging, LTP induction protocols The Journal of neuroscience High 17122039
2006 Targeted deletion of Kv4.2 eliminates fast transient outward K+ current (Ito,f) in mouse ventricular myocytes, with compensatory upregulation of slow Ito (Kv1.4-encoded) and dramatic reduction of KChIP2 protein, but no ventricular hypertrophy, demonstrating Kv4.2 is essential for Ito,f and that loss of Ito,f per se is not pathological. Kv4.2 knockout mice, voltage-clamp of ventricular myocytes, Western blot, mRNA analysis Circulation research High 16293790
2006 GRK2 phosphorylates DREAM/KChIP3 at Ser-95; this phosphorylation blocks DREAM-mediated membrane trafficking of Kv4.2 without affecting Kv4.2 tetramerization. Calcineurin de-phosphorylates GRK2-phosphorylated DREAM in vitro, and calcineurin inhibitors also block DREAM-mediated Kv4.2 surface expression. In vitro kinase assay, site-directed mutagenesis (S95D phosphomimetic), surface expression assay, calcineurin in vitro dephosphorylation, pharmacological inhibitors The Journal of biological chemistry High 17102134
2006 In Kv4.2 knockout mice, KChIP expression is reduced in a region- and cell-specific pattern that precisely follows normal Kv4.2 expression levels, indicating that Kv4.2:KChIP association confers reciprocal stability on KChIP subunits. Immunohistochemistry on Kv4.2−/− mouse brains, region- and cell-specific analysis The Journal of neuroscience Medium 17122038
2007 Kv4.2 undergoes activity-dependent internalization from dendritic spines and dendrites upon glutamate receptor stimulation in hippocampal neurons; internalization is clathrin-mediated and requires NMDA receptor activation and Ca2+ influx. LTP induced by glycine application causes synaptic insertion of GluR1 simultaneously with Kv4.2 internalization. Live imaging of EGFP-Kv4.2, whole-cell patch clamp, pharmacological blockade (clathrin inhibitors, NMDA antagonists, Ca2+ chelation), hippocampal slice cultures Neuron High 17582333
2007 SAP97 interacts with Kv4.2 via the C-terminus of Kv4.2 and the PDZ domains of SAP97; SAP97 directs Kv4.2 to the postsynaptic density and spines; CaMKII-dependent phosphorylation of SAP97 regulates subcellular localization of Kv4.2. Co-immunoprecipitation, PSD fractionation, lentiviral RNAi of SAP97, pharmacological SAP97 translocation assay, immunocytochemistry in hippocampal neurons The Journal of biological chemistry High 17635915
2007 mGlu5 activation leads to ERK-mediated phosphorylation of Kv4.2 at Ser616 in spinal cord dorsal horn neurons, inhibiting A-type K+ currents and increasing neuronal excitability; Kv4.2 S616A mutant analysis and Kv4.2 knockout mice confirm this specific residue and channel are required for mGlu5-induced nociceptive behavior. Site-directed mutagenesis (S616A), whole-cell patch clamp in dorsal horn neurons, Kv4.2 knockout mice, pharmacological ERK inhibition, behavioral assays The Journal of neuroscience High 18045912
2008 PKA activation induces Kv4.2 internalization from dendritic spines in hippocampal neurons; PKA inhibition prevents AMPA-induced internalization; a point mutation at Kv4.2 S552A (C-terminal PKA site) prevents AMPA-induced internalization, establishing that PKA phosphorylation at S552 is required for activity-dependent Kv4.2 trafficking. Live imaging of EGFP-Kv4.2, pharmacological PKA activation/inhibition (forskolin, 8-Br-cAMP, H89), site-directed mutagenesis (S552A), hippocampal neuron transfection The Journal of neuroscience High 18650329
2008 Gating charge (Q) immobilization in Kv4.2 at hyperpolarized voltages has the same kinetics and voltage dependence as closed-state inactivation, and both are independent of the N-terminal region; a CTX-blocked Kv4.2 channel was used to isolate gating currents, establishing that Q-immobilization and closed-state inactivation are two manifestations of the same voltage sensor desensitization process. Gating current measurements using CTX-blocked engineered Kv4.2 channels, two-electrode voltage clamp, kinetic modeling The Journal of general physiology High 18299396
2008 ISA channels are complexes of four Kv4.2 and four DPP6 subunits; stoichiometry established by tandem-subunit constructs enforcing 4:4 and 4:2 assemblies and by direct amino acid analysis of purified complexes. Tandem-subunit constructs, protein purification, direct amino acid analysis, biophysical characterization The Journal of biological chemistry High 18364354
2009 DPP6-S co-expression with Kv4.2 increases the unitary conductance of Kv4.2 channels from ~4 pS to ~7.5 pS (matching native CGN channels); CGN Kv4 channels from dpp6 knockout mice have conductance indistinguishable from Kv4.2 alone; charge-neutralization mutations in two N-terminal acidic residues of DPP6-S eliminate this increase, implicating electrostatic interactions. Single-channel recordings in heterologous cells and native CGNs, dpp6 knockout mice, site-directed mutagenesis of DPP6-S The Journal of neuroscience High 19279261
2009 S4-S5 linker residues (including Glu323) and S6 residue Val404 are critical for Kv4.2 closed-state inactivation; alanine-scanning mutagenesis and double-mutant cycle analysis demonstrate dynamic coupling between voltage sensors and the cytoplasmic gate underlies closed-state inactivation. Alanine-scanning mutagenesis of S4-S5 linker/S5/S6, two-electrode voltage clamp in Xenopus oocytes, double-mutant cycle analysis, selective redox modulation of double-cysteine mutants The Journal of general physiology High 19171772
2009 PKC directly phosphorylates Kv4.2 C-terminus at Ser447 and Ser537 in vitro; phosphorylation at Ser537 is increased in hippocampus upon PKC activation; mutation of both PKC sites to alanine increases surface expression of Kv4.2. Furthermore, prior PKC phosphorylation enhances subsequent ERK phosphorylation of Kv4.2 in vitro, establishing Kv4.2 as a locus for PKC-ERK cross-talk. In vitro PKC kinase assay with GST-fusion proteins, site-directed mutagenesis, surface biotinylation, phospho-selective antibody, in vitro sequential kinase assay The Biochemical journal High 18795890
2009 CaV3.1 (T-type Ca2+ channel) associates with the Kv4.2-KChIP3-DPP10c complex and Ca2+ entry through CaV3.1 shifts Kv4.2 inactivation voltage; this regulation is selective to CaV3 isoforms and not observed with CaV1.4, CaV2.1, or CaV2.3. Co-expression in heterologous cells, electrophysiology, calcium channel pharmacology Channels (Austin, Tex.) Medium 20458163
2010 KChIP4a enhances stabilization and membrane expression of Kv4.2 via a mechanism requiring PKA phosphorylation of Kv4.2 at S552; other KChIP isoforms enhance Kv4.2 surface expression and stability without requiring S552 phosphorylation. A-kinase anchoring proteins (AKAPs) are identified as Kv4.2 binding partners. Co-immunoprecipitation, surface biotinylation, pulse-chase stability assays, site-directed mutagenesis (S552A), co-expression in hippocampal neurons Molecular and cellular neurosciences High 20045463
2010 Glutamate-induced downregulation of Kv4.2 is mediated specifically by NR2B-containing extrasynaptic NMDA receptors (not synaptic NMDA receptors); Ca2+ influx through NR2B-NMDA receptors activates calpain, which degrades Kv4.2 protein, reducing Kv4.2 clusters and causing a hyperpolarizing shift in A-current inactivation. Whole-cell patch clamp, immunocytochemistry, Western blot, pharmacological NR2B antagonists, calpain inhibitors, selective synaptic vs. extrasynaptic NMDA receptor stimulation protocols Neuroscience High 19857555
2011 Quantitative immunogold freeze-fracture replica labeling (SDS-FRL) reveals only ~70% increase in Kv4.2 immunogold density along the proximo-distal axis of CA1 apical dendrites (not the 6-fold gradient predicted by electrophysiology), found similarly in main apical dendrites, oblique dendrites, and dendritic spines; no Kv4.2 labeling in presynaptic axons. SDS-digested freeze-fracture replica labeling (SDS-FRL), high-resolution quantitative immunogold EM, confirmed with Kv4.2−/− tissue as negative control The European journal of neuroscience High 22098631
2012 DPP6 expression in mouse cortex is unaffected by Kv4.2 and/or Kv4.3 deletion, and DPP6/DPP10 localize to the cell surface independently of Kv4.2; DPP6/DPP10 selectively stabilize cell-surface Kv4.2 protein without affecting total or surface DPP6/DPP10 levels; further addition of KChIP3 in the presence of DPP10 markedly increases both total and surface Kv4.2. Kv4.2/Kv4.3 knockout mice, Western blot, surface biotinylation, heterologous co-expression The Journal of biological chemistry High 22311982
2014 A de novo KCND2 missense mutation (p.Val404Met) found in twins with autism and epilepsy causes significantly slowed inactivation of Kv4.2 channels, either alone or co-expressed with wild-type, consistent with dominant gain-of-function; the effect on closed-state inactivation is preserved in the presence of auxiliary subunits. Whole-exome sequencing, heterologous expression in HEK cells, whole-cell patch clamp, wild-type/mutant co-expression Human molecular genetics High 24501278
2015 PACAP/PAC1 receptor activation leads to phosphorylation of Kv4.2 and downregulation of surface channel density via convergent PKA and ERK1/2 signaling; PKA-induced effects on Kv4.2 require ERK1/2 phosphorylation of the channel at two specific residues but not direct PKA phosphorylation, establishing a GPCR-channel signaling cascade. Whole-cell patch clamp in hippocampal neurons, surface biotinylation, pharmacological inhibitors of PKA and ERK, identification of phosphorylation sites Neuropharmacology Medium 26456351
2015 H2S inhibits Kv4.2-mediated Ito by targeting a Cys320/Cys529 disulfide motif; mutation of either residue blocks the H2S effect; H2S breaks the disulfide bridge between oxidized cysteine residues but does not modify single cysteines, establishing a specific redox regulatory mechanism. Site-directed mutagenesis (C320A, C529A), whole-cell patch clamp in cardiomyocytes and heterologous cells, pharmacological H2S application Antioxidants & redox signaling High 25756524
2016 miR-324-5p directly inhibits Kv4.2 protein expression by binding to KCND2 mRNA (recruited to RISC after status epilepticus); antagonizing miR-324-5p is seizure-suppressive and neuroprotective in wild-type but not Kcnd2 knockout mice, placing miR-324-5p-mediated Kv4.2 silencing in the seizure onset pathway. RISC immunoprecipitation, miRNA mimic/antagomir transfection, in vivo kainic acid seizure model, Kcnd2 knockout genetic epistasis, Western blot Cell reports High 27681419
2018 The V404M (Val404Met) mutation in Kv4.2 specifically enhances closed-state inactivation (CSI) of channels that have not opened while profoundly impairing inactivation of channels that have opened; the mutation increases stability of the inactivated state and slows closure of open channels (required for CSI); the larger volume of methionine vs valine is a major factor; physical coupling between voltage sensor and pore gate is maintained in the inactivated state. Whole-cell patch clamp in Xenopus oocytes with detailed kinetic analysis, comparison of closed-state vs open-state inactivation, auxiliary subunit co-expression, structural interpretation Proceedings of the National Academy of Sciences of the United States of America High 29581270
2018 A gain-of-function KCND2 mutation p.S447R causes nocturnal paroxysmal atrial fibrillation; the mutation increases the Kv4.2 inactivation time constant and impairs PKC-dependent regulation of Kv4.2 membrane expression (S447 is a PKC phosphorylation site), resulting in augmented channel surface expression and enhanced Ito in both homotetrameric Kv4.2 and heterotetrameric Kv4.2-Kv4.3 channels. Whole-exome sequencing, linkage analysis, Xenopus oocyte electrophysiology, co-expression of mutant and wild-type, hybrid Kv4.2-Kv4.3 chimeric channels Circulation. Genomic and precision medicine High 30571183
2020 Activity-induced phosphorylation of Kv4.2 at pThr607-Pro triggers binding of Pin1 (peptidyl-prolyl cis-trans isomerase), which isomerizes Kv4.2 at this motif, causing dissociation of the Kv4.2-DPP6 complex; mice with Kv4.2 T607A knock-in show altered Kv4.2-DPP6 interaction, increased A-type K+ current, reduced CA1 pyramidal neuron excitability, and improved reversal learning. Pin1 binding assays, Kv4.2 T607A knock-in mice, co-immunoprecipitation, whole-cell patch clamp in CA1 neurons, Morris water maze and lever press behavioral assays Nature communications High 32218435
2020 GSK3β directly phosphorylates Kv4.2 at Ser616 in nucleus accumbens medium spiny neurons; GSK3β-mediated phosphorylation inhibits Kv4.2 channel activity and underlies augmented spike-timing-dependent LTP in chronic mild stress mice; GSK3β knockdown prevents both LTP changes and depressive-like behavior. AAV2-shRNA knockdown of GSK3β, whole-cell patch clamp, immunohistochemistry, pharmacological Kv4.2 inhibition, biochemical phosphorylation analysis Proceedings of the National Academy of Sciences of the United States of America High 32209671
2005 The N-terminal proximal region (residues 11-23) of Kv4.2 is the major KChIP interaction site; T1 domain residues and C-terminal truncations also affect KChIP2 binding and gating modulation; binding and functional modulation are tightly coupled at the N-terminal site but more loosely coupled at T1 and C-terminal sites. Lysine-scanning and structure-based mutagenesis, co-immunoprecipitation, whole-cell patch clamp in mammalian cells The Journal of physiology High 16096338
2004 Mossy fiber synaptic contact and glutamatergic activity (NMDA and/or AMPA receptor activation) are required for targeting Kv4.2 channels from the soma to dendrites and synaptic sites in cerebellar granule cells; glutamate receptor activation in monocultures (without synapse formation) is sufficient to induce dendritic targeting. Co-culture of granule cells with pontine grey nucleus cells, confocal imaging, pharmacological blockade of NMDA/AMPA receptors Journal of neurochemistry Medium 15140189
2003 Actin depolymerization by cytochalasin D increases Kv4.2 current density ~7-fold in HEK cells by increasing the number and focal clustering of channels at the cell surface, without changing voltage dependence, single-channel conductance, or open probability. Whole-cell and single-channel patch clamp, cytochalasin D treatment, surface imaging, confocal microscopy in HEK cells American journal of physiology. Heart and circulatory physiology Medium 14551056
2009 DPPX-S co-expression with Kv4.2 causes a −26 mV shift in the gating charge-voltage relationship and accelerates outward gating charge movement; DPPX-S has no effect on Shaker B gating currents, establishing that DPPX-S specifically remodels Kv4.2 voltage-sensor dynamics through destabilization of resting/intermediate states. Gating current measurements (CTX-blocked engineered Kv4.2 channel system), two-electrode voltage clamp in Xenopus oocytes The Journal of general physiology High 17130523
2009 DPPX-S and KChIP auxiliary subunits, despite distinct structures, exert similar effects on Kv4.2 trafficking (releasing ER retention, promoting plasma membrane expression, altering phosphorylation and stability); KChIP4a inhibits both DPPX-S and other KChIP effects, consistent with ternary complex formation early in biosynthesis; tandem MS reveals co-expression with either DPPX-S or KChIP2 generates similar Kv4.2 phosphorylation patterns matching brain. Heterologous co-expression, Western blot, immunofluorescence, tandem mass spectrometry phosphoproteomics Biochemistry High 19441798

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Regulation of dendritic excitability by activity-dependent trafficking of the A-type K+ channel subunit Kv4.2 in hippocampal neurons. Neuron 278 17582333
2006 Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 272 17122039
2012 Encephalitis and antibodies to dipeptidyl-peptidase-like protein-6, a subunit of Kv4.2 potassium channels. Annals of neurology 253 23225603
2003 A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels. The Journal of biological chemistry 219 12829703
2000 The A-type potassium channel Kv4.2 is a substrate for the mitogen-activated protein kinase ERK. Journal of neurochemistry 214 11080179
1998 Somatodendritic depolarization-activated potassium currents in rat neostriatal cholinergic interneurons are predominantly of the A type and attributable to coexpression of Kv4.2 and Kv4.1 subunits. The Journal of neuroscience : the official journal of the Society for Neuroscience 187 9547221
2005 ERK/MAPK regulates the Kv4.2 potassium channel by direct phosphorylation of the pore-forming subunit. American journal of physiology. Cell physiology 145 16251476
2001 minK-related peptide 1 associates with Kv4.2 and modulates its gating function: potential role as beta subunit of cardiac transient outward channel? Circulation research 145 11375270
1997 Suppression of neuronal and cardiac transient outward currents by viral gene transfer of dominant-negative Kv4.2 constructs. The Journal of biological chemistry 142 9395498
2000 Kv4.2 mRNA abundance and A-type K(+) current amplitude are linearly related in basal ganglia and basal forebrain neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 141 10632587
2004 Calcium-calmodulin-dependent kinase II modulates Kv4.2 channel expression and upregulates neuronal A-type potassium currents. The Journal of neuroscience : the official journal of the Society for Neuroscience 136 15071113
1999 Kvbeta1.2 subunit coexpression in HEK293 cells confers O2 sensitivity to kv4.2 but not to Shaker channels. The Journal of general physiology 131 10352037
2005 Targeted deletion of Kv4.2 eliminates I(to,f) and results in electrical and molecular remodeling, with no evidence of ventricular hypertrophy or myocardial dysfunction. Circulation research 129 16293790
2004 Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10). Biophysical journal 117 15454437
2005 Multiprotein assembly of Kv4.2, KChIP3 and DPP10 produces ternary channel complexes with ISA-like properties. The Journal of physiology 116 16123112
2000 Localization and enhanced current density of the Kv4.2 potassium channel by interaction with the actin-binding protein filamin. The Journal of neuroscience : the official journal of the Society for Neuroscience 115 11102480
2001 Kinetic analysis of open- and closed-state inactivation transitions in human Kv4.2 A-type potassium channels. The Journal of physiology 110 11507158
2000 Kv4.2 phosphorylation by cyclic AMP-dependent protein kinase. The Journal of biological chemistry 108 10681507
2007 Metabotropic glutamate receptor 5 modulates nociceptive plasticity via extracellular signal-regulated kinase-Kv4.2 signaling in spinal cord dorsal horn neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 100 18045912
2006 A Kv4.2 truncation mutation in a patient with temporal lobe epilepsy. Neurobiology of disease 98 16934482
2001 Hippocampal heterotopia lack functional Kv4.2 potassium channels in the methylazoxymethanol model of cortical malformations and epilepsy. The Journal of neuroscience : the official journal of the Society for Neuroscience 98 11517252
1997 Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current. Cardiovascular research 92 9093524
2014 Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation. Human molecular genetics 91 24501278
2003 Differential recruitment of Kv1.4 and Kv4.2 to lipid rafts by PSD-95. The Journal of biological chemistry 90 14559911
1997 Decreased expression of Kv4.2 and novel Kv4.3 K+ channel subunit mRNAs in ventricles of renovascular hypertensive rats. Circulation research 90 9314834
1999 Regional contributions of Kv1.4, Kv4.2, and Kv4.3 to transient outward K+ current in rat ventricle. The American journal of physiology 88 10330244
1997 Clustering of KV4.2 potassium channels in postsynaptic membrane of rat supraoptic neurons: an ultrastructural study. Neuroscience 88 9070739
2005 A role for Kif17 in transport of Kv4.2. The Journal of biological chemistry 85 16257958
2002 PKA modulation of Kv4.2-encoded A-type potassium channels requires formation of a supramolecular complex. The Journal of neuroscience : the official journal of the Society for Neuroscience 81 12451113
2008 Electrical remodelling maintains firing properties in cortical pyramidal neurons lacking KCND2-encoded A-type K+ currents. The Journal of physiology 77 18187474
2016 MicroRNA-Mediated Downregulation of the Potassium Channel Kv4.2 Contributes to Seizure Onset. Cell reports 76 27681419
2008 Protein kinase a mediates activity-dependent Kv4.2 channel trafficking. The Journal of neuroscience : the official journal of the Society for Neuroscience 75 18650329
2008 Ternary Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule neurons. The Journal of physiology 71 18276729
2006 Differential expression of I(A) channel subunits Kv4.2 and Kv4.3 in mouse visual cortical neurons and synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 17122053
2000 Input-specific immunolocalization of differentially phosphorylated Kv4.2 in the mouse brain. Learning & memory (Cold Spring Harbor, N.Y.) 67 11040264
2008 Altered phosphorylation and localization of the A-type channel, Kv4.2 in status epilepticus. Journal of neurochemistry 65 18513371
2002 Cell surface targeting and clustering interactions between heterologously expressed PSD-95 and the Shal voltage-gated potassium channel, Kv4.2. The Journal of biological chemistry 64 11923279
2009 Kv4.2 knockout mice demonstrate increased susceptibility to convulsant stimulation. Epilepsia 62 19453702
2006 Unanticipated region- and cell-specific downregulation of individual KChIP auxiliary subunit isotypes in Kv4.2 knock-out mouse brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 17122038
1991 Functional characterization of RK5, a voltage-gated K+ channel cloned from the rat cardiovascular system. FEBS letters 61 1722463
2010 Molecular dissection of I(A) in cortical pyramidal neurons reveals three distinct components encoded by Kv4.2, Kv4.3, and Kv1.4 alpha-subunits. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 20371829
2016 MiR-223-3p as a Novel MicroRNA Regulator of Expression of Voltage-Gated K+ Channel Kv4.2 in Acute Myocardial Infarction. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 54 27322747
2003 Ito channels are octomeric complexes with four subunits of each Kv4.2 and K+ channel-interacting protein 2. The Journal of biological chemistry 53 14623880
2006 G protein-coupled receptor kinase 2-mediated phosphorylation of downstream regulatory element antagonist modulator regulates membrane trafficking of Kv4.2 potassium channel. The Journal of biological chemistry 52 17102134
2005 Contribution of N- and C-terminal Kv4.2 channel domains to KChIP interaction [corrected]. The Journal of physiology 52 16096338
2012 Kv4.2 knockout mice have hippocampal-dependent learning and memory deficits. Learning & memory (Cold Spring Harbor, N.Y.) 50 22505720
2006 Differential modulation of Kv4.2 and Kv4.3 channels by calmodulin-dependent protein kinase II in rat cardiac myocytes. American journal of physiology. Heart and circulatory physiology 50 16648177
2002 Prevention of hypertrophy by overexpression of Kv4.2 in cultured neonatal cardiomyocytes. Circulation 50 12403671
2012 Neuritin activates insulin receptor pathway to up-regulate Kv4.2-mediated transient outward K+ current in rat cerebellar granule neurons. The Journal of biological chemistry 49 23066017
1999 Characterization of human Kv4.2 mediating a rapidly-inactivating transient voltage-sensitive K+ current. Receptors & channels 47 10551270
1996 Reverse use dependence of Kv4.2 blockade by 4-aminopyridine. The Journal of pharmacology and experimental therapeutics 47 8930194
2009 Dynamic coupling of voltage sensor and gate involved in closed-state inactivation of kv4.2 channels. The Journal of general physiology 46 19171772
2009 The dipeptidyl-peptidase-like protein DPP6 determines the unitary conductance of neuronal Kv4.2 channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 45 19279261
2013 MicroRNA-301a mediated regulation of Kv4.2 in diabetes: identification of key modulators. PloS one 44 23573265
2014 Evaluation of genes encoding for the transient outward current (Ito) identifies the KCND2 gene as a cause of J-wave syndrome associated with sudden cardiac death. Circulation. Cardiovascular genetics 43 25214526
2006 Calcineurin increases cardiac transient outward K+ currents via transcriptional up-regulation of Kv4.2 channel subunits. The Journal of biological chemistry 43 17060317
2012 Differential dorso-ventral distributions of Kv4.2 and HCN proteins confer distinct integrative properties to hippocampal CA1 pyramidal cell distal dendrites. The Journal of biological chemistry 42 22511771
2007 SAP97 directs the localization of Kv4.2 to spines in hippocampal neurons: regulation by CaMKII. The Journal of biological chemistry 42 17635915
2011 Unique somato-dendritic distribution pattern of Kv4.2 channels on hippocampal CA1 pyramidal cells. The European journal of neuroscience 41 22098631
2000 Voltage-gated K(+)Channel, Kv4.2, localizes predominantly to the transverse-axial tubular system of the rat myocyte. Journal of molecular and cellular cardiology 40 10860776
2018 Kv4.2 autism and epilepsy mutation enhances inactivation of closed channels but impairs access to inactivated state after opening. Proceedings of the National Academy of Sciences of the United States of America 39 29581270
2008 Gating charge immobilization in Kv4.2 channels: the basis of closed-state inactivation. The Journal of general physiology 39 18299396
1998 Regulation of Kv4.2 and Kv1.4 K+ channel expression by myocardial hypertrophic factors in cultured newborn rat ventricular cells. Journal of molecular and cellular cardiology 39 9710812
2020 Activity-dependent isomerization of Kv4.2 by Pin1 regulates cognitive flexibility. Nature communications 37 32218435
2010 KChIP4a regulates Kv4.2 channel trafficking through PKA phosphorylation. Molecular and cellular neurosciences 37 20045463
2011 Metabotropic glutamate receptor 5 regulates excitability and Kv4.2-containing K⁺ channels primarily in excitatory neurons of the spinal dorsal horn. Journal of neurophysiology 36 21451053
2010 Regulation of the KV4.2 complex by CaV3.1 calcium channels. Channels (Austin, Tex.) 36 20458163
2006 A dipeptidyl aminopeptidase-like protein remodels gating charge dynamics in Kv4.2 channels. The Journal of general physiology 36 17130523
2009 Kv4.2 is a locus for PKC and ERK/MAPK cross-talk. The Biochemical journal 35 18795890
2003 GATA and FOG2 transcription factors differentially regulate the promoter for Kv4.2 K(+) channel gene in cardiac myocytes and PC12 cells. Cardiovascular research 35 14613857
2020 Chronic mild stress alters synaptic plasticity in the nucleus accumbens through GSK3β-dependent modulation of Kv4.2 channels. Proceedings of the National Academy of Sciences of the United States of America 34 32209671
2001 Different effects of the Ca(2+)-binding protein, KChIP1, on two Kv4 subfamily members, Kv4.1 and Kv4.2. FEBS letters 34 11423117
1999 Expression of Kv3.1 and Kv4.2 genes in developing cerebellar granule cells. Developmental neuroscience 34 10449980
2003 Dihydropyridine Ca2+ channel antagonists and agonists block Kv4.2, Kv4.3 and Kv1.4 K+ channels expressed in HEK293 cells. British journal of pharmacology 33 12788813
2009 Expression and localization of voltage dependent potassium channel Kv4.2 in epilepsy associated focal lesions. Neurobiology of disease 32 19596445
2008 I SA channel complexes include four subunits each of DPP6 and Kv4.2. The Journal of biological chemistry 32 18364354
2016 Neuritin Up-regulates Kv4.2 α-Subunit of Potassium Channel Expression and Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-NFATc4 Signaling Pathway. The Journal of biological chemistry 31 27307045
2008 Interaction between transcription factors Iroquois proteins 4 and 5 controls cardiac potassium channel Kv4.2 gene transcription. Cardiovascular research 31 18815185
1997 Kainic acid-induced generalized seizures alter the regional hippocampal expression of the rat Kv4.2 potassium channel gene. Neuroscience letters 31 9302094
2019 Expression, Cellular and Subcellular Localisation of Kv4.2 and Kv4.3 Channels in the Rodent Hippocampus. International journal of molecular sciences 30 30634540
2013 Neuregulin-1/ErbB4 signaling regulates Kv4.2-mediated transient outward K+ current through the Akt/mTOR pathway. American journal of physiology. Cell physiology 29 23703525
2004 Mossy fibre contact triggers the targeting of Kv4.2 potassium channels to dendrites and synapses in developing cerebellar granule neurons. Journal of neurochemistry 29 15140189
2003 Quantitative relationship between Kv4.2 mRNA and A-type K+ current in rat striatal cholinergic interneurons during development. Journal of neurophysiology 29 12843309
2018 Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales-Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.2. Frontiers in neural circuits 28 29467627
2018 Nocturnal Atrial Fibrillation Caused by Mutation in KCND2, Encoding Pore-Forming (α) Subunit of the Cardiac Kv4.2 Potassium Channel. Circulation. Genomic and precision medicine 28 30571183
2012 Augmentation of Kv4.2-encoded currents by accessory dipeptidyl peptidase 6 and 10 subunits reflects selective cell surface Kv4.2 protein stabilization. The Journal of biological chemistry 28 22311982
2009 Arachidonic acid potently inhibits both postsynaptic-type Kv4.2 and presynaptic-type Kv1.4 IA potassium channels. The European journal of neuroscience 28 19453640
2010 Downregulation of Kv4.2 channels mediated by NR2B-containing NMDA receptors in cultured hippocampal neurons. Neuroscience 27 19857555
2010 High-mobility group box 1 (HMGB1) downregulates cardiac transient outward potassium current (Ito) through downregulation of Kv4.2 and Kv4.3 channel transcripts and proteins. Journal of molecular and cellular cardiology 27 20483361
2006 Pituitary adenylate cyclase activating polypeptide reduces expression of Kv1.4 and Kv4.2 subunits underlying A-type K(+) current in adult mouse olfactory neuroepithelia. Neuroscience 27 16426762
2015 Convergent phosphomodulation of the major neuronal dendritic potassium channel Kv4.2 by pituitary adenylate cyclase-activating polypeptide. Neuropharmacology 26 26456351
2014 Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2. American journal of physiology. Heart and circulatory physiology 26 24486512
2004 Modulation of Kv4.2 channels by a peptide isolated from the venom of the giant bird-eating tarantula Theraphosa leblondi. Toxicon : official journal of the International Society on Toxinology 26 15208026
2015 Hydrogen Sulfide Targets the Cys320/Cys529 Motif in Kv4.2 to Inhibit the Ito Potassium Channels in Cardiomyocytes and Regularizes Fatal Arrhythmia in Myocardial Infarction. Antioxidants & redox signaling 25 25756524
2008 Regulation of Kv4.2 channels by glutamate in cultured hippocampal neurons. Journal of neurochemistry 25 18363830
2009 Convergent modulation of Kv4.2 channel alpha subunits by structurally distinct DPPX and KChIP auxiliary subunits. Biochemistry 24 19441798
2021 Long noncoding RNA FAM66C promotes tumor progression and glycolysis in intrahepatic cholangiocarcinoma by regulating hsa-miR-23b-3p/KCND2 axis. Environmental toxicology 23 34418280
2018 Kv4.2 channel activity controls intrinsic firing dynamics of arcuate kisspeptin neurons. The Journal of physiology 23 29214635
2003 Effects of flecainide and quinidine on Kv4.2 currents: voltage dependence and role of S6 valines. British journal of pharmacology 23 12721103
2003 Increased focal Kv4.2 channel expression at the plasma membrane is the result of actin depolymerization. American journal of physiology. Heart and circulatory physiology 23 14551056

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