Affinage

KCNA4

Potassium voltage-gated channel subfamily A member 4 · UniProt P22459

Round 2 corrected
Length
653 aa
Mass
73.3 kDa
Annotated
2026-04-28
130 papers in source corpus 52 papers cited in narrative 52 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNA4 (Kv1.4) is a voltage-gated potassium channel that conducts a rapidly inactivating A-type K+ current, playing key roles in cardiac repolarization (slow-recovering Ito,s), presynaptic regulation of hippocampal LTP, nociceptor excitability, and circadian clock period modulation (PMID:2001794, PMID:10330244, PMID:9844011, PMID:26152125). The channel undergoes fast N-type inactivation via a ball-and-chain mechanism at the N-terminus coupled to slower C-type inactivation at the extracellular pore (involving H508 and K532), with C-type inactivation serving as the rate-limiting step for recovery; these two inactivation processes are allosterically linked through the cytoplasmic S6 segment (PMID:8788936, PMID:12388308, PMID:14608006). Channel gating is dynamically regulated by CaMKII/calcineurin phosphorylation of N-terminal residues, PKA phosphorylation at Ser229, and redox modification of N-terminal cysteines, while surface expression and clustering depend on PSD-95 PDZ2-mediated binding to the C-terminal ETDV motif, palmitoylation-dependent lipid raft recruitment, Kvβ subunit-assisted trafficking, and a pore-region/VXXSL dual determinant (PMID:9133364, PMID:16000151, PMID:8584439, PMID:7477295, PMID:14559911, PMID:11024060, PMID:12901718). Loss-of-function mutation p.Arg89Gln causes an autosomal recessive syndrome of congenital cataract, striatal abnormality, and intellectual disability (PMID:27582084).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1991 High

    Molecular cloning and functional expression established that KCNA4 encodes a rapidly inactivating, 4-AP-sensitive voltage-gated K+ channel, defining its biophysical identity within the Shaker family.

    Evidence cDNA cloning from human ventricle, Xenopus oocyte two-electrode voltage clamp

    PMID:1986382 PMID:2001794

    Open questions at the time
    • No structural model of the full-length channel
    • Subunit stoichiometry of native channels unknown
  2. 1993 High

    Demonstration that a single Kv1.4 subunit confers rapid inactivation on heteromeric Kv1.1/1.2/1.5 complexes explained how native A-type currents with intermediate kinetics arise from mixed-subunit assemblies.

    Evidence Co-injection of cRNAs in Xenopus oocytes with functional voltage clamp characterization

    PMID:8495559 PMID:8661510

    Open questions at the time
    • Native subunit stoichiometry not determined at single-channel level
    • Heteromer assembly rules beyond pairwise not established
  3. 1995 High

    Dissection of inactivation gating revealed that N-type (ball-and-chain) and C-type (pore) inactivation are coupled, with C-type inactivation as the rate-limiting step for recovery, resolving a longstanding question about why Kv1.4 recovery is much slower than N-type inactivation alone predicts.

    Evidence N-terminal deletion mutagenesis and voltage-sensor mutations in Xenopus oocytes

    PMID:8788936

    Open questions at the time
    • Structural basis of C-type inactivation at the pore not visualized
    • Coupling mechanism between N-type ball and C-type gate at atomic resolution unknown
  4. 1995 High

    PSD-95 was identified as the scaffolding partner that clusters Kv1.4 at the cell surface via PDZ-domain binding to the channel's C-terminal ETDV motif, establishing a paradigm for synaptic K+ channel localization.

    Evidence Yeast two-hybrid, co-immunoprecipitation, heterologous cell co-expression, and immunofluorescence clustering

    PMID:7477295 PMID:8938729

    Open questions at the time
    • In vivo disruption of PSD-95–Kv1.4 interaction not performed genetically
    • Whether PSD-95 clustering alters channel biophysics in neurons unresolved
  5. 1997 High

    CaMKII phosphorylation of N-terminal residues was shown to slow inactivation and accelerate recovery, while calcineurin-mediated dephosphorylation restores fast inactivation, establishing Ca²⁺-dependent bidirectional regulation of Kv1.4 gating.

    Evidence Direct enzyme application to Kv1.4-expressing Xenopus oocytes with voltage clamp

    PMID:9133364

    Open questions at the time
    • Exact phosphorylation site(s) not identified by mass spectrometry
    • In vivo physiological context of CaMKII regulation not tested
  6. 1998 High

    Ultrastructural localization placed Kv1.4 at presynaptic axons and boutons in hippocampus, and antisense knockdown eliminated both early- and late-phase LTP at CA1, establishing a presynaptic role in synaptic plasticity.

    Evidence Immunogold electron microscopy and in vivo antisense knockdown with electrophysiology

    PMID:9437018 PMID:9844011

    Open questions at the time
    • Antisense approach lacks genetic specificity; conditional knockout confirmation absent
    • Mechanism by which presynaptic Kv1.4 regulates LTP induction not defined
  7. 1998 High

    Palmitoylation of PSD-95 N-terminal cysteines was found to be required for in vivo interaction with Kv1.4 and subsequent lipid raft recruitment, linking post-translational modification of the scaffold to channel microdomain targeting.

    Evidence Metabolic [³H]palmitate labeling, Cys3/5 mutagenesis, co-immunoprecipitation, later confirmed by raft fractionation from rat brain

    PMID:14559911 PMID:9459448

    Open questions at the time
    • Whether raft localization affects Kv1.4 single-channel conductance or open probability not tested
    • Enzyme(s) catalyzing PSD-95 palmitoylation not identified in these studies
  8. 2000 High

    Identification of H508 and K532 as extracellular pore residues governing pH-sensitive C-type inactivation, and V561 as the intracellular S6 residue allosterically coupled to the outer pore, defined the transmembrane communication pathway regulating recovery kinetics.

    Evidence Site-directed mutagenesis with ion-substitution and pH experiments in Xenopus oocytes

    PMID:10896716 PMID:12388308 PMID:14608006

    Open questions at the time
    • No crystal or cryo-EM structure of Kv1.4 to validate structural interpretation
    • Role of these residues in native cardiac or neuronal context not confirmed
  9. 2000 High

    Combined genetic elimination of Kv4.2-mediated Ito,f and Kv1.4-mediated Ito,s in mice caused severe arrhythmias (QT prolongation, VT), proving that Kv1.4 encodes the slow-recovering transient outward current and that both Ito components are essential for cardiac repolarization.

    Evidence Kv4.2W362F transgenic × Kv1.4−/− knockout mice with telemetric ECG and patch clamp

    PMID:10884375

    Open questions at the time
    • Human cardiac relevance not directly tested; species differences in Ito composition exist
    • Compensatory remodeling in double-mutant mice not fully characterized
  10. 2001 High

    Kvβ2 was shown to enhance Kv1.4 surface expression through an NADPH-binding-dependent mechanism distinct from its kinetic modulation of inactivation, separating the β-subunit's oxidoreductase-like chaperone function from its direct gating effects.

    Evidence Mutagenesis of Kvβ2 NADPH-binding and catalytic sites with co-expression in oocytes and Western blot of protein levels

    PMID:11024060

    Open questions at the time
    • Whether Kvβ2 acts as a true oxidoreductase on Kv1.4 or functions as a chaperone through NADPH-induced conformation unknown
    • No in vivo trafficking assay
  11. 2003 High

    Identification of a pore-region determinant and a C-terminal VXXSL motif as interdependent trafficking signals resolved how Kv1.4 achieves efficient cell-surface expression while the highly homologous Kv1.1 is retained in the ER.

    Evidence Chimeric Kv1.4/Kv1.1 channels, VXXSL deletion, surface biotinylation

    PMID:12901718 PMID:14688283

    Open questions at the time
    • Coat protein or adaptor recognizing VXXSL not identified
    • Contribution of glycosylation versus VXXSL in native neurons not dissected
  12. 2005 High

    PKA phosphorylation at Ser229 in the T1 domain was identified as a neuronal-activity-dependent mechanism reducing Kv1.4 current density, adding a second kinase-based regulatory axis complementary to CaMKII-mediated gating modulation.

    Evidence Phospho-Ser229-specific antibody in cultured cortical neurons, in vitro kinase assay, S229A mutagenesis with electrophysiology

    PMID:16000151

    Open questions at the time
    • Whether Ser229 phosphorylation affects surface expression, open probability, or both not distinguished
    • Downstream physiological consequence (e.g. firing rate change) not measured
  13. 2011 High

    Sequential immunoprecipitation from human CNS tissue mapped native Kv1.4-containing heteromeric complexes — including Kv1.3/1.4/1.1/1.2 tetramers in grey matter and Kv1.1/1.4 dimers in white matter — providing the first systematic view of Kv1.4 heteromeric composition in the human brain.

    Evidence Sequential immunoprecipitation from human autopsy tissue with subunit-specific antibodies

    PMID:10428084

    Open questions at the time
    • Stoichiometry within individual tetramers not determined
    • Functional properties of specific native heteromers not reconstituted
  14. 2015 High

    Kv1.4 knockout shortened circadian period by ~0.5 h and reduced PER2 expression period in SCN, revealing an unexpected feedback from membrane excitability (IA) onto the molecular clock.

    Evidence Kcna4−/− mice crossed with PER2::LUC reporter, SCN explant bioluminescence, wheel-running activity

    PMID:26152125

    Open questions at the time
    • Signal transduction pathway from Kv1.4 current to PER2 transcription not identified
    • Whether this is a direct cell-autonomous effect or network-level phenomenon not resolved
  15. 2016 High

    The p.Arg89Gln loss-of-function variant was identified as the cause of an autosomal recessive syndrome of congenital cataract, striatal thinning, and intellectual disability, establishing the first human Mendelian disease linked to KCNA4.

    Evidence Autozygosity mapping, whole-exome sequencing, functional expression of R89Q in Xenopus oocytes showing reduced current

    PMID:27582084

    Open questions at the time
    • Only one family reported; independent replication in additional families not yet published
    • Mechanism linking Kv1.4 loss-of-function to cataract formation not elucidated
  16. 2019 High

    IL-6/gp130 signaling was shown to downregulate Kv1.4 in nociceptors, and Kv1.4 antisense knockdown phenocopied vibration-induced hyperalgesia, mechanistically linking cytokine-driven Kv1.4 suppression to pain sensitization.

    Evidence Rat vibration model with anti-IL-6 antibody rescue, Kv1.4 antisense knockdown in DRG, gp130 conditional knockdown

    PMID:31335655

    Open questions at the time
    • Whether Kv1.4 downregulation is transcriptional or post-transcriptional not determined
    • Relevance to chronic pain syndromes in humans not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution structure of Kv1.4 exists, the precise mechanism linking N-terminal ball binding at S6 to outer-pore C-type inactivation conformational change remains structurally unresolved, and the signaling pathway by which Kv1.4 current feeds back onto PER2 transcription in the SCN is unknown.
  • No cryo-EM or crystal structure of Kv1.4 homomeric or heteromeric channel
  • Structural basis of N-type/C-type inactivation coupling not visualized
  • Molecular link between Kv1.4-mediated IA and circadian clock gene expression unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 6 GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-382551 Transport of small molecules 5 R-HSA-162582 Signal Transduction 4 R-HSA-9909396 Circadian clock 1
Partners
ACTN2DLG1DLG4KCNA1KCNA2KCNAB1KCNAB2KCNAB3
Complex memberships
Kv1 heteromultimeric channel complexKv1.4/Kvβ complex

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 KCNA4 (HK1/hPCN2) was molecularly cloned from human ventricle and functionally expressed in Xenopus oocytes, demonstrating it encodes a rapidly inactivating voltage-gated K+ channel with sensitivity to 4-aminopyridine. cDNA cloning, Xenopus oocyte expression, two-electrode voltage clamp FASEB journal High 2001794
1991 The hPCN1 isoform (related to KCNA4) expressed in Xenopus oocytes produces a slowly inactivating outward K+ current inhibited by 4-aminopyridine, establishing the electrophysiological signature of human Shaker-family channels including Kv1.4. cDNA isolation, Xenopus oocyte expression, two-electrode voltage clamp Proceedings of the National Academy of Sciences High 1986382
1993 Kv1.4 co-assembles with non-inactivating Kv1 subunits (Kv1.1, Kv1.2, Kv1.5) to form heteromultimeric channels; a single inactivating Kv1.4 subunit is sufficient to confer inactivation on the heteromeric complex, and hybrid channels display recovery kinetics closer to native cardiac transient outward current. Co-injection of cRNAs in Xenopus oocytes, two-electrode voltage clamp Circulation research High 8495559
1994 The mouse Kcna4/Kv1.4 gene is contained in a single coding exon encoding a 654-amino-acid protein; the 5' NCR contains SP1 repeats and lacks TATA box; ATTTA repeats in the 3' NCR of the longer transcript reduce translational efficiency; the gene maps to mouse chromosome 2 and human chromosome 11p14. Genomic cloning, sequencing, Xenopus oocyte expression, in situ hybridization, fluorescence mapping Genomics High 8020965
1995 C-type inactivation governs recovery from inactivation in Kv1.4: removal of the N-terminal ball domain (fast inactivation) revealed a slow C-type inactivation process, and recovery rates from N-type and C-type inactivated states are nearly identical, indicating C-type inactivation is the rate-limiting step for recovery. N-terminal deletion mutagenesis, Xenopus oocyte two-electrode voltage clamp, site-directed mutagenesis of S4 voltage sensor (R454Q) The Journal of physiology High 8788936
1995 Kv beta 3 co-expressed with Kv1.4 alpha-subunit accelerates both fast and slow components of inactivation, increases contribution of the slow inactivation component, slows recovery from inactivation (for intact Kv1.4 but not N-terminal deletion mutant), and slows deactivation, demonstrating that beta subunits modulate post-activation channel states. Xenopus oocyte co-expression, two-electrode voltage clamp The American journal of physiology High 7631872
1995 PSD-95 family MAGUKs cluster Kv1.4 at the cell surface through direct binding of the channel's C-terminal cytoplasmic tail to PDZ domains of PSD-95, establishing the PDZ-mediated clustering mechanism for Shaker-type K+ channels. Yeast two-hybrid, co-immunoprecipitation, heterologous cell co-expression, immunofluorescence clustering assay Nature High 7477295
1996 The C-terminal -ETDV sequence of Kv1.4 is required for binding to and clustering with SAP97 and PSD-95; mutation of this motif abolishes both binding and clustering; PSD-95 induces cell-surface plaque-like clusters while SAP97 causes intracellular aggregates, demonstrating differential clustering activity of MAGUK family members. C-terminal deletion mutagenesis, heterologous cell co-expression, immunofluorescence Neuropharmacology High 8938729
1996 Oxidizing cysteine-modifying reagents (DTBNP, chloramine-T) remove N-type inactivation of Kv1.4 and slow deactivation, effects reversed by DTT, indicating that redox state of cysteine residue(s) in the N-terminal inactivation domain regulates channel gating. Whole-cell patch clamp in HEK-293 cells expressing rat Kv1.4, cysteine-specific oxidizing/reducing agents Pflugers Archiv Medium 8584439
1996 The mouse Kv1.4 transcription unit produces two mRNAs (3.5 kb and 4.5 kb) from a common start site; ATTTA repeats in the 3' NCR of the longer transcript reduce translational efficiency ~4–5-fold compared with the shorter transcript; the basal promoter is GC-rich with SP1 repeats and lacks tissue specificity. 5' RACE, reporter assays, Xenopus oocyte expression of individual transcripts The Journal of biological chemistry Medium 8663090
1997 CaMKII phosphorylation of an N-terminal residue of Kv1.4 slows inactivation gating and accelerates recovery from N-type inactivation; dephosphorylation by calcineurin accelerates inactivation 5–10-fold and promotes cumulative inactivation; the balance is regulated by intracellular Ca2+ concentration, making Kv1.4 inactivation Ca2+-sensitive. Xenopus oocyte expression, two-electrode voltage clamp, CaMKII and calcineurin application, frequency-dependent stimulation protocols The Journal of neuroscience High 9133364
1997 Kvbeta1.1 and Kvbeta2.1 subunits accelerate Kv1.4 activation kinetics without altering voltage dependence of activation or steady-state inactivation; Kvbeta2.1 modestly lengthens the slow time constant of recovery from inactivation. Xenopus oocyte co-expression, two-electrode voltage clamp Pflugers Archiv Medium 9359902
1997 A truncated Kv1.1 polypeptide (Kv1.1N206Tag) forms heteromultimeric complexes with native Kv1.4 and Kv1.5 in GH3 cells and is retained in the endoplasmic reticulum, providing a dominant-negative mechanism for long QT syndrome by trapping native channels in the ER. Double immunoprecipitation with channel-specific antibodies, subcellular fractionation, immunofluorescence/confocal colocalization, RNase protection assay The Journal of biological chemistry High 9334228
1996 N-type inactivation in Kv1.4 requires only a single inactivating subunit in heteromultimers; the proximal N-terminal region is critical; large deletions in the linker between the inactivation region and first transmembrane domain do not affect inactivation rate, suggesting the inactivation particle remains near the permeation pathway in the open state. Xenopus oocyte expression of Kv1.4-Kv1.5 tandems and co-expressed subunits, N-terminal deletion mutagenesis, two-electrode voltage clamp The Journal of membrane biology High 8661510
1998 PSD-95 is palmitoylated on N-terminal cysteines 3 and 5, which is required for its partitioning as an integral membrane protein and for PDZ-mediated interaction with Kv1.4 in vivo; palmitoylation-deficient PSD-95 mutants fail to interact with Kv1.4 in living cells. Metabolic labeling with [3H]palmitate, mutagenesis of Cys3/Cys5, cell fractionation, co-immunoprecipitation Neuron High 9459448
1998 Kv1.4-containing channels are localized presynaptically on axons and near excitatory synaptic boutons in hippocampal perforant path and mossy fiber regions, as determined by immunofluorescence and ultrastructural immunogold electron microscopy. Confocal immunofluorescence, electron microscopic immunocytochemistry with anti-Kv1.4 antibody The Journal of neuroscience High 9437018
1998 Targeted deletion of Kv1.4 in mice does not eliminate the rapidly inactivating transient outward current (Ito) in adult ventricular myocytes; Kv4 subfamily channels are not upregulated in knockout mice, indicating Kv1.4 is not the primary molecular basis of Ito in adult murine ventricle. Targeted gene disruption (knockout mice), whole-cell patch clamp of isolated ventricular myocytes, Western blot The Journal of physiology High 9547391
1998 Kvbeta1.2 has three separable effects on Kv1.4: (1) a current-enhancing effect via the C-terminus, (2) allosteric enhancement of N-type inactivation by the alpha-ball, and (3) direct open-channel block by the beta-ball; the alpha-beta interaction is restricted to the N-terminus of Kv1.4 and C-terminus of Kvbeta1.2, with no direct interaction between the Kv1.4 alpha-ball and the Kvbeta subunit. Xenopus oocyte co-expression, two-electrode voltage clamp, N-terminal deletion mutants of Kv1.4, Kvbeta domain deletion mutants, yeast two-hybrid The Journal of physiology High 9763623
1998 Antisense knockdown of Kv1.4 in rat hippocampus eliminates both early- and late-phase LTP and reduces paired-pulse facilitation in CA1 neurons without affecting spatial memory or dentate gyrus LTP, demonstrating a presynaptic role for Kv1.4 in CA1 LTP. Intraventricular antisense oligodeoxyribonucleotide injection, RT-PCR, Western blot, in vivo electrophysiology, Morris water maze behavioral testing Proceedings of the National Academy of Sciences Medium 9844011
1999 N-terminal cysteines 3 and 5 of PSD-95 are essential for PSD-95 self-association (multimerization) and formation of cell-surface clusters with Kv1.4, but not for membrane association or binary binding to Kv1.4; multimerization is required for ternary complex formation with Kv1.4 and Fasciclin II. Mutagenesis of PSD-95 N-terminal cysteines, heterologous cell co-expression, immunofluorescence clustering assay, co-immunoprecipitation The Journal of biological chemistry High 9867876
1999 Regional differences in rat ventricular Ito are explained by differential expression of Kv1.4 (encoding slow-recovering Ito) and Kv4.2/Kv4.3 (encoding fast-recovering Ito); Kv1.4 protein and mRNA correlate with slow Ito density, and Kv1.4 kinetics in heterologous cells match slow Ito in myocytes. Western blot, Northern blot, patch clamp of ventricular myocytes and tsa-201 cells expressing individual channel subunits The American journal of physiology High 10330244
1999 Kv1 channel subunit composition determines surface expression: homotetrameric Kv1.4 localizes to the cell surface, while Kv1.1 is retained in ER; heteromeric assembly with Kv1.4 increases surface expression of Kv1.1 and Kv1.2 in a dose-dependent manner; Kvbeta subunits promote surface expression of each Kv1 complex. Transfection of mammalian cells and hippocampal neurons, immunofluorescence, surface biotinylation, Western blot The Journal of biological chemistry High 10896669
2000 Acidosis inhibits Kv1.4 during repetitive pulsing by slowing recovery from N-type inactivation; protonation of extracellular histidine H508 enhances C-type inactivation, which in turn slows recovery from N-type inactivation; elevated [K+]o and the K532Y mutation also abolish the slowing effect, linking extracellular pore gating to N-type inactivation recovery. Xenopus oocyte two-electrode voltage clamp, site-directed mutagenesis (H508Q, K532Y), N-terminal deletion mutants, ion substitution experiments The Journal of physiology High 10896716
2000 PSD-95 clustering completely suppresses Kv1.4 internalization (t1/2 = 87 min when alone); a non-clustering mutant C35S-PSD-95 enhances internalization rate (t1/2 = 16 min); clustering is necessary and sufficient for internalization suppression, revealing a new role for PSD-95 in stabilizing channels at the cell surface. Cell-surface biotinylation assay in transfected HEK293 cells, GFP-tagged Kv1.4 co-expression, electrophysiology The Journal of biological chemistry High 10625685
2000 Genetic elimination of both Ito,f (Kv4.2W362F dominant-negative) and Ito,s (Kv1.4 knockout) in mice causes marked QT prolongation, atrioventricular block, ventricular tachycardia, and early afterdepolarizations, demonstrating that upregulation of Kv1.4 underlies the slow Ito in Kv4.2W362F-expressing ventricles and that both currents together are required for normal cardiac electrical function. Transgenic/knockout mouse cross (Kv4.2W362F x Kv1.4-/-), in vivo telemetric ECG, patch clamp of isolated ventricular myocytes, histology, echocardiography Circulation research High 10884375
2000 ACTH potently and rapidly reduces Kv1.4 mRNA expression in bovine adrenal zona fasciculata cells (t1/2 ~1 h, IC50 ~1.2 pM) via a cAMP/PKA-partially dependent mechanism, leading to decreased A-type current over 72 h, demonstrating pretranslational regulation of Kv1.4 by the hypothalamic-pituitary-adrenal axis. cDNA cloning from bovine adrenal cortex, quantitative mRNA analysis, whole-cell patch clamp, cAMP analog and PKA inhibitor experiments The Journal of biological chemistry Medium 10913143
2001 The N-terminus of Kv1.4 (and Kv1.5) binds to the internal spectrin repeats of alpha-actinin-2; this interaction is specific (not observed for Kv1.1, 1.2, or 1.3); the Kv1.5 binding region maps to residues 73–148 of the N-terminus; calmodulin does not affect this interaction. Yeast two-hybrid analysis, in vitro GST pulldown binding assays, N-terminal deletion mapping FEBS letters Medium 11389904
2001 The PDZ2 domain of PSD-95 is required for efficient clustering of Kv1.4; the position of PDZ2 in full-length PSD-95 is also prerequisite for normal cluster formation; PDZ1 dysfunction does not impair clustering, revealing that high-affinity PDZ2-ligand binding and correct multi-domain architecture both determine clustering efficiency. Site-directed mutagenesis of individual PDZ domains in full-length PSD-95, PDZ inversion constructs, COS-1 cell co-expression, immunofluorescence clustering assay The Journal of biological chemistry High 11723117
2001 Riluzole irreversibly slows Kv1.4 inactivation (tau_i from 29 to 623 ms) by an oxidative, voltage-dependent mechanism: the effect is blocked by reducing agents (glutathione, DTT) and absent when applied at depolarized holding potentials, implicating a cysteine in the N-terminal inactivation domain as the target; riluzole also reversibly inhibits Kv1.4 current (IC50 = 70 μM) by a separate mechanism. Whole-cell patch clamp in bovine adrenal zona fasciculata cells, antioxidant and non-hydrolyzable ATP controls, holding potential manipulation The Journal of pharmacology and experimental therapeutics Medium 11561084
2001 Kv beta 2 enhances Kv1.4 current amplitude and accelerates inactivation; mutations in Kv beta 2 that disrupt the NADPH binding or catalytic site abolish the expression-enhancing effect but not the acceleration of inactivation, suggesting that the oxidoreductase activity of Kv beta 2 is required for correct processing/surface expression of Kv1.4 but not for modulation of inactivation kinetics. Xenopus oocyte co-expression, two-electrode voltage clamp, site-directed mutagenesis of Kvbeta2 NADPH-binding and catalytic sites, Western blot of Kv1.4 protein levels, yeast two-hybrid The Journal of biological chemistry High 11024060
2002 C-type inactivation of Kv1.4 is sensitive to extracellular K+ (inhibited by elevated [K+]o), intracellular K+ (removal speeds C-type inactivation), and extracellular pH via histidine H508; a V561A mutation on the intracellular side of S6 inverts the C-type inactivation relationship with [K+]o; K532Y mutation slows C-type inactivation and abolishes pH dependence, demonstrating transmembrane communication between intracellular S6 and extracellular pore mouth in regulating inactivation. Xenopus oocyte two-electrode voltage clamp, N-terminal deletion mutant (fKv1.4ΔN), site-directed mutagenesis (V561A, K532Y, H508), ion substitution American journal of physiology. Heart and circulatory physiology High 12388308
2003 N-glycosylation of Kv1.4 (but not Kv1.1) promotes protein stability and cell-surface trafficking; preventing glycosylation decreases Kv1.4 protein stability, causes intracellular retention, and reduces surface expression; a pore region determinant determines whether glycosylation positively or negatively affects trafficking, and this determinant can be transferred to chimeric Kv1.1 proteins. Glycosylation inhibitors and site-directed mutagenesis of glycosylation sites in Kv1.1 and Kv1.4, chimeric channel constructs, surface biotinylation, immunofluorescence, Western blot The Journal of biological chemistry High 14688283
2003 PSD-95 palmitoylation is required to recruit Kv1.4 (but not Kv4.2) into lipid rafts; co-expression of PSD-95 increases raft-associated Kv1.4; deletion of the Kv1.4 C-terminal PSD-95 binding motif or substitution of palmitoylation-deficient PSD-95 eliminates raft recruitment, providing the first evidence that PSD-95 binding recruits Kv channels into lipid raft microdomains. Detergent-resistant membrane fractionation from rat brain, heterologous co-expression, lipid raft patching, immunostaining, deletion and palmitoylation mutants The Journal of biological chemistry High 14559911
2003 Kv1.4 cell-surface trafficking requires both a pore region determinant and a C-terminal VXXSL motif; removing VXXSL inhibits surface expression only when the Kv1.4 pore is present; the relevant subregion maps to a threonine residue in the deep pore; these two trafficking determinants act interdependently. Chimeric channel constructs between Kv1.4 and Kv1.1 pore regions, VXXSL deletion and truncation mutants, surface biotinylation, immunofluorescence in transfected cells The Biochemical journal High 12901718
2003 C-type inactivation in Kv1.4 involves allosteric coupling between the N-terminal inactivation ball or lipophilic compounds (like quinidine) and the cytoplasmic half of S6; binding of the N-terminal domain or quinidine to S6 shifts the channel into a conformation resembling the C-type inactivated state; the V561A mutation reduces affinity for both quinidine and the N-terminal domain, confirming S6 as part of the N-terminal binding site. Xenopus oocyte two-electrode voltage clamp, N-terminal deletion + V561A double mutant, quinidine pharmacology, varied [K+]o The Journal of physiology High 14608006
2003 Arachidonic acid and other cis-unsaturated fatty acids inhibit Kv1.4 current and accelerate inactivation in native bovine adrenal zona fasciculata cells; lysophospholipids activate the co-expressed TREK-1 channel but do not affect Kv1.4; ETYA also inhibits Kv1.4, indicating direct lipid modulation independent of active AA metabolites. Whole-cell patch clamp in native bovine AZF cells, fatty acid/lysophospholipid application, ETYA control The Journal of membrane biology Medium 14724761
2004 An extracellular lysine residue K532 in Kv1.4 acts as a 'guard' regulating K+ access to the selectivity filter; mutation K532Y abolishes both K+ activation and C-type inactivation; protonation of H508 at acidic pH also abolishes K+ activation, indicating that extracellular charges regulate selectivity filter open probability. Xenopus oocyte two-electrode voltage clamp, site-directed mutagenesis (K532, H508), varied [K+]o and pH Biophysical journal High 15454439
2005 Neuronal transmission (via NMDA receptor Ca2+ influx) stimulates PKA phosphorylation of Kv1.4 at Ser229 in the T1 domain; glutamate, high K+, or K+ channel blockers increase Ser229 phosphorylation; TTX or Ca2+ depletion reduces it; Ser229Ala mutation enhances current density, indicating phosphorylation at this site reduces Kv1.4 channel activity. In vitro kinase assay, Western blot with phospho-Ser229-specific antibody in cultured rat cortical neurons, mutagenesis (Ser229Ala), pharmacological manipulation of neurotransmission Journal of neurochemistry High 16000151
2005 EA1 mutations in KCNA1 (E325D, V404I, V408A, I177N) that line the pore or S1 segment of Kv1.1 alter fast inactivation of heteromeric Kv1.4-Kv1.1/Kvbeta1.1 and Kvbeta1.2 channels by decreasing rate and degree of N-type inactivation and accelerating recovery from inactivation; Kvbeta1.1/1.2 subunits regulate the proportion of wild-type Kv1.4-Kv1.1 channels available to open. Tandem-linked Kv1.4-Kv1.1 constructs expressed in Xenopus oocytes, two-electrode voltage clamp, EA1 point mutations The European journal of neuroscience High 17156368
2006 DPP10 modulates Kv1.4 inactivation similarly to its known effects on Kv4.3: co-expression causes faster time to peak current and negatively shifts half-inactivation potential; however, DPP10 slows rather than speeds recovery from inactivation in Kv1.4, demonstrating DPP10 as a general modulator of voltage-gated K+ channel inactivation acting on different inactivation states than KChIP2b. Xenopus oocyte co-expression, two-electrode voltage clamp, DPP10 transmembrane domain truncation mutants American journal of physiology. Cell physiology Medium 16738002
2006 EA1 mutation F184C in Kv1.1 sensitizes heteromeric Kv1.4-Kv1.1/Kvbeta1.1 channels to Zn2+: the complex has high-affinity (<10 μM) and low-affinity (<0.5 mM) Zn2+ binding sites; F184C decreases equilibrium dissociation constants for both sites, slows activation, increases time-to-peak, decreases N-type inactivation rate, and slows repriming compared with wild-type channels. Tandem Kv1.4-Kv1.1 constructs in Xenopus oocytes, two-electrode voltage clamp, Zn2+ dose-response, F184C mutation American journal of physiology. Cell physiology High 16956965
2007 Ginsenoside Rg3 inhibits Kv1.4 channel current by interacting with residue Lys531; K531Y mutation abolishes the Rg3 effect; elevated [K+]o reduces Rg3 inhibition; Rg3 shifts K+ activation curve rightward and competes with TEA, with molecular docking showing hydrogen bonds between Rg3 and Lys531. Xenopus oocyte expression, two-electrode voltage clamp, site-directed mutagenesis (K531Y and others), K+ and TEA competition experiments, molecular docking Molecular pharmacology Medium 17959711
2007 Kv1.4 is re-expressed in oligodendrocyte precursor cells (AN2-positive) and premyelinating oligodendrocytes during experimental autoimmune encephalomyelitis but not in mature oligodendrocytes or healthy adult spinal cord; Kv1.4-positive cells are actively proliferating and ensheathing naked axons, suggesting a role in oligodendroglial cell cycle progression during remyelination. Confocal immunofluorescence with cell-type markers, in vitro oligodendrocyte precursor culture, proliferation assays, ciliary neurotrophic factor knockout mice The American journal of pathology Medium 17600124
2009 Arachidonic acid (1 pM intracellular) inhibits Kv1.4-mediated IA by >50% and shifts voltage dependence of inactivation by -9 mV; Trolox C (antioxidant) slows AA effects on amplitude and shifts Kv1.4 activation by -32 mV, implicating an oxidative mechanism; these effects are direct on the channel alpha-subunit. Whole-cell voltage clamp of HEK293 cells transfected with Kv1.4 or Kv4.2 rat cDNA, intracellular AA application, Trolox C antioxidant controls The European journal of neuroscience Medium 19453640
2010 In cortical pyramidal neurons, Kv1.4, Kv4.2, and Kv4.3 encode distinct components of macroscopic IA; in cells lacking both Kv4.2 and Kv4.3, Kv1.4 encodes a minor but ubiquitous IA component; loss of individual subunits causes Kv alpha-subunit-specific electrical remodeling. Single and double knockout mice (Kv1.4-/-, Kv4.2-/-, Kv4.3-/-), whole-cell patch clamp of cortical pyramidal neurons, 4-AP pharmacology The Journal of neuroscience High 20371829
2011 Kv1.4 and Kv1.5 associate with native Kv1 heteromultimers in human CNS; sequential immunoprecipitation identifies a Kv1.3/1.4/1.1/1.2 tetramer in grey matter, Kv1.1/1.4 dimers in white matter and spinal cord, and apparent Kv1.4 homotetramers in all CNS regions, with Kvbeta1.1 coprecipitating with all alpha subunits in white matter. Sequential immunoprecipitation from human autopsy tissue (cerebral grey/white matter, spinal cord) with subunit-specific antibodies, immunoblotting Journal of neurochemistry High 10428084
2011 A model of Kv1.4 inactivation demonstrates that N- and C-type inactivation are coupled through direct transitions between N- and C-type inactivated states; C-type inactivation begins at lower-voltage pre-activated states while N-type is coupled to the open state; C-type inactivation is the rate-limiting step for recovery, and a model with only distinct inactivated states without cross-transitions cannot reproduce experimental data. Two-electrode voltage clamp of Kv1.4 and Kv1.4ΔN in Xenopus oocytes, K532Y mutation, computational Markov chain modeling constrained by experimental data Biophysical journal High 21190652
2013 Spinal cord injury in rats reduces Kv1.4 protein and mRNA expression in bladder afferent neurons, accompanied by decreased A-type K+ current density and a hyperpolarizing shift in KA inactivation, resulting in increased nociceptor excitability with lower spike thresholds and tonic firing. Whole-cell patch clamp of dissociated L6-S1 DRG neurons, immunohistochemistry, real-time PCR, spinal transection model The Journal of urology Medium 23896350
2014 Nociceptor-specific deletion of gp130 (IL-6 signal transducer) in SNS-gp130-/- mice increases A-type K+ currents and Kcna4 (Kv1.4) mRNA levels in sensory neurons, reducing excitability, suggesting IL-6/gp130 signaling normally suppresses Kv1.4 expression and thereby promotes nociceptor excitability. Conditional knockout mice, whole-cell patch clamp, TaqMan RT-PCR for Kcna4 and other ion channel mRNAs, action potential recording Pflugers Archiv Medium 24463703
2015 Loss of Kv1.4 (Kcna4-/-) shortens circadian period in SCN firing and locomotor activity by ~0.5 h and reduces PER2 expression period in SCN explants; combined loss of Kv1.4 and Kv4.2 advances daily activity onset by ~1.8 h in a light cycle, demonstrating that IA channels encoded by Kv1.4 feed back onto molecular clock (PER2) expression. Kv1.4-/- and Kv4.2-/- knockout mice crossed with Per2Luc reporter mice, SCN explant bioluminescence imaging, wheel-running locomotor activity recording Journal of biological rhythms High 26152125
2016 A missense variant p.Arg89Gln in KCNA4 causes a novel autosomal recessive syndrome with congenital cataract, striatal thinning, intellectual disability, and ADHD; the R89Q mutant produces significantly lower current amplitude than wild-type in Xenopus oocytes, and co-expression of wild-type and mutant results in intermediate current, indicating loss-of-function; KCNA4 mRNA is expressed in mouse brain, lens, and retina, and Kv1.4 co-localizes with cholinergic amacrine and rod bipolar cells. SNP arrays, autozygosity mapping, whole-exome sequencing, two-electrode voltage clamp in Xenopus oocytes, RT-PCR, immunohistochemistry Journal of medical genetics High 27582084
2019 IL-6 downregulates Kv1.4 expression in dorsal root ganglion nociceptors via gp130/IL-6 receptor signaling, causing muscle hyperalgesia in a rat vibration model; antisense knockdown of Kv1.4 in DRG mimics vibration-induced muscle hyperalgesia; anti-IL-6 antibody attenuates both hyperalgesia and Kv1.4 downregulation. Rat hindlimb vibration model, local neutralizing anti-IL-6 injection, Kv1.4 antisense knockdown in DRG, gp130 knockdown, immunohistochemistry, behavioral pain testing Pain High 31335655

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
1995 Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature 895 7477295
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2005 International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacological reviews 721 16382104
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1996 Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases. The Journal of neuroscience : the official journal of the Society for Neuroscience 627 8601796
1997 GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules. The Journal of cell biology 444 9024696
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation. Cell reports 327 26119735
1998 CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90. Neuron 264 9581762
1998 N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron 257 9459448
1991 Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 221 2001794
1980 Establishment of a cell line (NPC/HK1) from a differentiated squamous carcinoma of the nasopharynx. International journal of cancer 210 6259064
1998 Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule-associated protein 1A. The Journal of neuroscience : the official journal of the Society for Neuroscience 165 9786987
1993 Heteromultimeric assembly of human potassium channels. Molecular basis of a transient outward current? Circulation research 156 8495559
2000 Subunit composition determines Kv1 potassium channel surface expression. The Journal of biological chemistry 151 10896669
2000 Functional consequences of elimination of i(to,f) and i(to,s): early afterdepolarizations, atrioventricular block, and ventricular arrhythmias in mice lacking Kv1.4 and expressing a dominant-negative Kv4 alpha subunit. Circulation research 140 10884375
1997 Frequency-dependent inactivation of mammalian A-type K+ channel KV1.4 regulated by Ca2+/calmodulin-dependent protein kinase. The Journal of neuroscience : the official journal of the Society for Neuroscience 137 9133364
1999 Subunit composition of Kv1 channels in human CNS. Journal of neurochemistry 135 10428084
1996 Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases. Neuropharmacology 129 8938729
2002 Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102. The Journal of biological chemistry 124 11937501
2021 Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers. Nature genetics 116 34857952
2014 Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes. Proceedings of the National Academy of Sciences of the United States of America 114 24550280
1998 Presynaptic localization of Kv1.4-containing A-type potassium channels near excitatory synapses in the hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 112 9437018
2022 HK1 from hepatic stellate cell-derived extracellular vesicles promotes progression of hepatocellular carcinoma. Nature metabolism 103 36192599
2001 Interaction of gamma 1-syntrophin with diacylglycerol kinase-zeta. Regulation of nuclear localization by PDZ interactions. The Journal of biological chemistry 103 11352924
1995 C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes. The Journal of physiology 101 8788936
2003 Glycosylation affects the protein stability and cell surface expression of Kv1.4 but Not Kv1.1 potassium channels. A pore region determinant dictates the effect of glycosylation on trafficking. The Journal of biological chemistry 94 14688283
2000 Internalization of the Kv1.4 potassium channel is suppressed by clustering interactions with PSD-95. The Journal of biological chemistry 94 10625685
1998 Mouse spermatogenic cell-specific type 1 hexokinase (mHk1-s) transcripts are expressed by alternative splicing from the mHk1 gene and the HK1-S protein is localized mainly in the sperm tail. Molecular reproduction and development 92 9508088
1998 The transient outward current in mice lacking the potassium channel gene Kv1.4. The Journal of physiology 92 9547391
2003 Differential recruitment of Kv1.4 and Kv4.2 to lipid rafts by PSD-95. The Journal of biological chemistry 90 14559911
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
1991 Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Proceedings of the National Academy of Sciences of the United States of America 87 1986382
2001 The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins. The Journal of biological chemistry 82 11278603
2014 Cr(VI) reduction and Cr(III) immobilization by Acinetobacter sp. HK-1 with the assistance of a novel quinone/graphene oxide composite. Environmental science & technology 80 25296002
2011 The hybrid histidine kinase Hk1 is part of a two-component system that is essential for survival of Borrelia burgdorferi in feeding Ixodes scapularis ticks. Infection and immunity 80 21606185
2008 Novel association of HK1 with glycated hemoglobin in a non-diabetic population: a genome-wide evaluation of 14,618 participants in the Women's Genome Health Study. PLoS genetics 77 19096518
1993 Shaker-related potassium channel, Kv1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv1.4 and Kv1.5 genes in myocardial development and hypertrophy. The Journal of clinical investigation 77 7691883
2004 An improved method for the synthesis of cellulose membrane-bound peptides with free C termini is useful for PDZ domain binding studies. Chemistry & biology 75 15123239
1999 Requirement of N-terminal cysteines of PSD-95 for PSD-95 multimerization and ternary complex formation, but not for binding to potassium channel Kv1.4. The Journal of biological chemistry 72 9867876
1998 Memory and long-term potentiation (LTP) dissociated: normal spatial memory despite CA1 LTP elimination with Kv1.4 antisense. Proceedings of the National Academy of Sciences of the United States of America 70 9844011
2003 Centrally administered hemokinin-1 (HK-1), a neurokinin NK1 receptor agonist, produces substance P-like behavioral effects in mice and gerbils. Neuropharmacology 69 12842130
2005 Novel autoantibodies to a voltage-gated potassium channel Kv1.4 in a severe form of myasthenia gravis. Journal of neuroimmunology 66 16182377
1999 Mutations in the KCNA1 gene associated with episodic ataxia type-1 syndrome impair heteromeric voltage-gated K(+) channel function. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 65 10428758
2020 BDNF corrects NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming through KLF2/HK1 pathway in vascular endothelial cells. Cellular signalling 61 33253911
2015 Interaction of Cr(VI) reduction and denitrification by strain Pseudomonas aeruginosa PCN-2 under aerobic conditions. Bioresource technology 57 25795449
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
2014 A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa. Investigative ophthalmology & visual science 55 25190649
1990 Human potassium channel genes: Molecular cloning and functional expression. Molecular and cellular neurosciences 55 19912772
2006 Uncovering quantitative protein interaction networks for mouse PDZ domains using protein microarrays. Journal of the American Chemical Society 54 16637659
2001 A discrete amino terminal domain of Kv1.5 and Kv1.4 potassium channels interacts with the spectrin repeats of alpha-actinin-2. FEBS letters 54 11389904
2013 Dominant form of congenital hyperinsulinism maps to HK1 region on 10q. Hormone research in paediatrics 52 23859901
2017 MiR-34a, as a suppressor, enhance the susceptibility of gastric cancer cell to luteolin by directly targeting HK1. Gene 50 29054762
2006 Episodic ataxia type 1 mutations in the KCNA1 gene impair the fast inactivation properties of the human potassium channels Kv1.4-1.1/Kvbeta1.1 and Kv1.4-1.1/Kvbeta1.2. The European journal of neuroscience 50 17156368
2020 Anti-inflammation activity of exopolysaccharides produced by a medicinal fungus Cordyceps sinensis Cs-HK1 in cell and animal models. International journal of biological macromolecules 49 32035153
2019 An HK2 Antisense Oligonucleotide Induces Synthetic Lethality in HK1-HK2+ Multiple Myeloma. Cancer research 49 30885978
1997 Serpin-derived peptide substrates for investigating the substrate specificity of human tissue kallikreins hK1 and hK2. The Journal of biological chemistry 47 9368023
2011 Anti-voltage-gated potassium channel Kv1.4 antibodies in myasthenia gravis. Journal of neurology 46 22167224
2001 Ligand binding of the second PDZ domain regulates clustering of PSD-95 with the Kv1.4 potassium channel. The Journal of biological chemistry 46 11723117
2000 Inhibition of the K+ channel kv1.4 by acidosis: protonation of an extracellular histidine slows the recovery from N-type inactivation. The Journal of physiology 44 10896716
2001 A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors. Proceedings of the National Academy of Sciences of the United States of America 41 11149959
1995 Time- and voltage-dependent modulation of a Kv1.4 channel by a beta-subunit (Kv beta 3) cloned from ferret ventricle. The American journal of physiology 41 7631872
2022 Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism. Nature genetics 40 36333503
2013 Hyperexcitability of bladder afferent neurons associated with reduction of Kv1.4 α-subunit in rats with spinal cord injury. The Journal of urology 40 23896350
2002 Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses. American journal of physiology. Cell physiology 40 11997254
2001 The PDZ1 domain of SAP90. Characterization of structure and binding. The Journal of biological chemistry 40 11744724
2003 SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism. FEBS letters 39 12860415
2001 Neuroprotective agent riluzole dramatically slows inactivation of Kv1.4 potassium channels by a voltage-dependent oxidative mechanism. The Journal of pharmacology and experimental therapeutics 39 11561084
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
2003 Modulation of native TREK-1 and Kv1.4 K+ channels by polyunsaturated fatty acids and lysophospholipids. The Journal of membrane biology 38 14724761
2014 A missense mutation in HK1 leads to autosomal dominant retinitis pigmentosa. Investigative ophthalmology & visual science 37 25316723
1997 A cellular model for long QT syndrome. Trapping of heteromultimeric complexes consisting of truncated Kv1.1 potassium channel polypeptides and native Kv1.4 and Kv1.5 channels in the endoplasmic reticulum. The Journal of biological chemistry 36 9334228
1994 Genomic organization, nucleotide sequence, biophysical properties, and localization of the voltage-gated K+ channel gene KCNA4/Kv1.4 to mouse chromosome 2/human 11p14 and mapping of KCNC1/Kv3.1 to mouse 7/human 11p14.3-p15.2 and KCNA1/Kv1.1 to human 12p13. Genomics 36 8020965
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
1996 Cysteine-modifying reagents alter the gating of the rat cloned potassium channel Kv1.4. Pflugers Archiv : European journal of physiology 33 8584439
2016 Effect of lentivirus-mediated shRNA inactivation of HK1, HK2, and HK3 genes in colorectal cancer and melanoma cells. BMC genetics 32 28105937
1995 Antiarrhythmic and bradycardic drugs inhibit currents of cloned K+ channels, KV1.2 and KV1.4. European journal of pharmacology 32 7589202
2015 NF-κB p65 Subunit Is Modulated by Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) in Nasopharyngeal Carcinoma HONE1 and HK1 Cells. PloS one 31 25974126
2006 DPP10 is an inactivation modulatory protein of Kv4.3 and Kv1.4. American journal of physiology. Cell physiology 31 16738002
2002 Regulation of N- and C-type inactivation of Kv1.4 by pHo and K+: evidence for transmembrane communication. American journal of physiology. Heart and circulatory physiology 31 12388308
1996 N-type inactivation in the mammalian Shaker K+ channel Kv1.4. The Journal of membrane biology 31 8661510
2003 Trafficking of Kv1.4 potassium channels: interdependence of a pore region determinant and a cytoplasmic C-terminal VXXSL determinant in regulating cell-surface trafficking. The Biochemical journal 30 12901718
1996 Characterization of the transcription unit of mouse Kv1.4, a voltage-gated potassium channel gene. The Journal of biological chemistry 30 8663090
2016 Potential application of aerobic denitrifying bacterium Pseudomonas aeruginosa PCN-2 in nitrogen oxides (NOx) removal from flue gas. Journal of hazardous materials 29 27469045
2003 Immunohistochemical localization of the voltage-gated potassium channel subunit Kv1.4 in the central nervous system of the adult rat. Journal of chemical neuroanatomy 29 14615029
1998 Functional expression of GFP-tagged Kv1.3 and Kv1.4 channels in HEK 293 cells. The European journal of neuroscience 29 9875368
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
2006 Curcumin potently blocks Kv1.4 potassium channels. Biochemical and biophysical research communications 28 16647042
2001 Mutations in the Kv beta 2 binding site for NADPH and their effects on Kv1.4. The Journal of biological chemistry 28 11024060
2014 Reduced excitability of gp130-deficient nociceptors is associated with increased voltage-gated potassium currents and Kcna4 channel upregulation. Pflugers Archiv : European journal of physiology 26 24463703
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 26 16426762
2023 Inhibiting mitochondrial inflammation through Drp1/HK1/NLRP3 pathway: A mechanism of alpinetin attenuated aging-associated cognitive impairment. Phytotherapy research : PTR 25 36772986
2006 Episodic ataxia type 1 mutation F184C alters Zn2+-induced modulation of the human K+ channel Kv1.4-Kv1.1/Kvbeta1.1. American journal of physiology. Cell physiology 25 16956965
2003 Inactivation and recovery in Kv1.4 K+ channels: lipophilic interactions at the intracellular mouth of the pore. The Journal of physiology 25 14608006
2018 Hexokinase 2 is targetable for HK1 negative, HK2 positive tumors from a wide variety of tissues of origin. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 24 29880505
1999 Co-localization of Shaker A-type K+ channel (Kv1.4) and AMPA-glutamate receptor (GluR4) immunoreactivities to dendrites of OFF-bipolar cells of goldfish retina. Journal of neurocytology 23 10573608
2023 Hydroxysafflor yellow A protects against colitis in mice by suppressing pyroptosis via inhibiting HK1/NLRP3/GSDMD and modulating gut microbiota. Toxicology and applied pharmacology 22 37001609
2003 Fluoxetine blocks cloned neuronal A-type K+ channels Kv1.4. Neuroreport 22 14663209
1998 Separable effects of human Kvbeta1.2 N- and C-termini on inactivation and expression of human Kv1.4. The Journal of physiology 22 9763623
1997 Modification of rat brain Kv1.4 channel gating by association with accessory Kvbeta1.1 and beta2.1 subunits. Pflugers Archiv : European journal of physiology 22 9359902
2015 IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Circadian Period of PER2 Expression in the Suprachiasmatic Nucleus. Journal of biological rhythms 21 26152125
2003 Differential inhibition of transient outward currents of Kv1.4 and Kv4.3 by endothelin. Biochemical and biophysical research communications 21 14521958
2000 A bovine adrenocortical Kv1.4 K(+) channel whose expression is potently inhibited by ACTH. The Journal of biological chemistry 21 10913143
2024 Oridonin inhibits bladder cancer survival and immune escape by covalently targeting HK1. Phytomedicine : international journal of phytotherapy and phytopharmacology 20 38367425
2016 KCNA4 deficiency leads to a syndrome of abnormal striatum, congenital cataract and intellectual disability. Journal of medical genetics 20 27582084
2013 Founder mutations in NDRG1 and HK1 genes are common causes of inherited neuropathies among Roma/Gypsies in Slovakia. Journal of applied genetics 20 23996628
2007 Ginsenoside Rg3 inhibits human Kv1.4 channel currents by interacting with the Lys531 residue. Molecular pharmacology 20 17959711
2022 KLF2 mediates the suppressive effect of BDNF on diabetic intimal calcification by inhibiting HK1 induced endothelial-to-mesenchymal transition. Cellular signalling 19 35364229
2004 K+ activation of kir3.1/kir3.4 and kv1.4 K+ channels is regulated by extracellular charges. Biophysical journal 19 15454439
1983 Chromosome localization of the genes for ENO1, HK1, ADK, ACP2, MPI, ITPA, ACON1 and α-GAL in the American mink (Mustela vison). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 19 24258481
2015 Structural characterization and modeling of the Borrelia burgdorferi hybrid histidine kinase Hk1 periplasmic sensor: A system for sensing small molecules associated with tick feeding. Journal of structural biology 17 26321039
2013 Characterization of histidine-aspartate kinase HK1 and identification of histidine phosphotransfer proteins as potential partners in a Populus multistep phosphorelay. Physiologia plantarum 17 23330606
2013 Fine mapping and identification of blast resistance gene Pi-hk1 in a broad-spectrum resistant japonica rice landrace. Phytopathology 17 23718837
1999 Anti-tumor effect of angiogenesis inhibitor TNP-470 on the human nasopharyngeal carcinoma cell line NPC/HK1. Oncology 17 10394123
2000 Subcellular compartmentalization of a potassium channel (Kv1.4): preferential distribution in dendrites and dendritic spines of neurons in the dorsal cochlear nucleus. The European journal of neuroscience 16 11122345
2020 Cytotoxic Activity of Boesenbergia rotunda Extracts against Nasopharyngeal Carcinoma Cells (HK1). Cardamonin, a Boesenbergia rotunda Constituent, Inhibits Growth and Migration of HK1 Cells by Inducing Caspase-Dependent Apoptosis and G2/M-Phase Arrest. Nutrition and cancer 15 32270712
2019 Fubp1 supports the lactate-Akt-mTOR axis through the upregulation of Hk1 and Hk2. Biochemical and biophysical research communications 15 30871777
2019 New Naphtho-γ-Pyrones Isolated from Marine-Derived Fungus Penicillium sp. HK1-22 and Their Antimicrobial Activities. Marine drugs 15 31159234
2007 Re-expression of a developmentally restricted potassium channel in autoimmune demyelination: Kv1.4 is implicated in oligodendroglial proliferation. The American journal of pathology 15 17600124
2005 Neuronal transmission stimulates the phosphorylation of Kv1.4 channel at Ser229 through protein kinase A1. Journal of neurochemistry 15 16000151
2022 Nivolumab-induced Myositis and Myocarditis with Positive Anti-titin Antibody and Anti-voltage-gated Potassium Channel Kv1.4 Antibody. Internal medicine (Tokyo, Japan) 14 35314545
2022 Artesunate Inhibits the Development of Esophageal Cancer by Targeting HK1 to Reduce Glycolysis Levels in Areas With Zinc Deficiency. Frontiers in oncology 14 35646662
2021 Isolation and Assessment of a Highly-Active Anti-Inflammatory Exopolysaccharide from Mycelial Fermentation of a Medicinal Fungus Cs-HK1. International journal of molecular sciences 14 33671052
2018 Protection of Bifidobacterial cells against antibiotics by a high molecular weight exopolysaccharide of a medicinal fungus Cs-HK1 through physical interactions. International journal of biological macromolecules 14 30036626
2016 Functional Divergence of Poplar Histidine-Aspartate Kinase HK1 Paralogs in Response to Osmotic Stress. International journal of molecular sciences 14 27941652
2023 ErbB2-upregulated HK1 and HK2 promote breast cancer cell proliferation, migration and invasion. Medical oncology (Northwood, London, England) 13 37079118
2019 Interleukin 6 decreases nociceptor expression of the potassium channel KV1.4 in a rat model of hand-arm vibration syndrome. Pain 13 31335655
2011 A model of the interaction between N-type and C-type inactivation in Kv1.4 channels. Biophysical journal 13 21190652