Affinage

KCNC1

Voltage-gated potassium channel KCNC1 · UniProt P48547

Length
511 aa
Mass
57.9 kDa
Annotated
2026-06-10
87 papers in source corpus 39 papers cited in narrative 40 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

KCNC1 encodes Kv3.1, a high-threshold, rapidly activating and deactivating voltage-gated potassium channel that drives fast action-potential repolarization and enables sustained high-frequency firing in fast-spiking neurons, including auditory brainstem and parvalbumin-positive interneurons (PMID:9547392, PMID:32331822). By producing rapid repolarization, Kv3.1 minimizes spike broadening and limits activity-dependent presynaptic Ca2+ influx, thereby shaping synaptic transmission and short-term plasticity (PMID:12930807, PMID:9801357). Channel gating is set post-translationally: constitutive casein kinase 2 phosphorylation maintains the high voltage threshold, while activity-driven PKC dephosphorylation increases current to facilitate high-frequency spiking (PMID:16136041, PMID:11160386). Kv3.1 assembles into homotetramers and heteromers with Kv3.2 and Kv3.4, and its two C-terminal splice isoforms (Kv3.1a/b) are differentially targeted to axonal versus somatodendritic membranes through electrostatic interactions in the splice domain that unmask an axonal targeting motif (PMID:12592408, PMID:12091563, PMID:22105078, PMID:10482766). The channel associates with auxiliary and partner proteins including MiRP2, OSP/claudin-11, and p11, and its surface abundance is controlled by trafficking and by UBR5-mediated ubiquitin-proteasomal degradation (PMID:12954870, PMID:16624990, PMID:32331822, PMID:38865078). Cryo-EM structures define a rotated zinc-containing T1 cytoplasmic domain that controls gating via interactions with S6T helices, and a modulator-binding site at the voltage-sensor–pore interface that overlaps a disease-mutation hotspot (PMID:35840580, PMID:36741467, PMID:37812700). Pathogenic KCNC1 variants cause progressive myoclonus epilepsy (MEAK) and developmental epileptic encephalopathy: the recurrent p.R320H acts by dominant-negative loss of function through slowed activation, other variants reduce current or surface expression, and select S6-region variants instead confer gain of function by shifting activation to hyperpolarized potentials (PMID:25401298, PMID:33735526, PMID:31353855, PMID:36419348, PMID:41705663).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1992 High

    Establishing that KCNC1 encodes a functional voltage-gated K+ channel was the foundational step, defining its biophysical identity and chromosomal locus.

    Evidence Heterologous expression in Xenopus oocytes with matched native T-lymphocyte channel properties and RT-PCR

    PMID:1400413

    Open questions at the time
    • Did not address neuronal function
    • No subunit composition or partners identified
  2. 1998 High

    Linking Kv3.1 to a high-threshold, fast K+ current resolved why fast-spiking neurons can follow high-frequency stimulation, defining the channel's core physiological role.

    Evidence Patch-clamp, TEA/DTX pharmacology, in situ hybridization and simulation in MNTB auditory neurons; complementary work in inferior colliculus, cochlear nucleus, and Aplysia neurons

    PMID:9465111 PMID:9547392 PMID:9786983 PMID:9801357

    Open questions at the time
    • Mechanism coupling repolarization to Ca2+ control inferred indirectly in some systems
    • Native subunit composition not fully defined
  3. 1999 High

    Demonstrating heteromeric assembly with Kv3.2 (and later Kv3.4) showed that native Kv3 currents arise from mixed tetramers, refining the molecular basis of fast-spiking currents.

    Evidence Co-IP from pallidal membranes with electrophysiology; co-assembly studies with Kv3.4 in heterologous and native systems

    PMID:10482766 PMID:12592408

    Open questions at the time
    • Stoichiometry of native heteromers not quantified
    • Region-specific subunit ratios unknown
  4. 2005 High

    Identifying CK2 and PKC phosphorylation as opposing regulators explained how Kv3.1 gating is dynamically tuned to neuronal activity rather than being static.

    Evidence Phosphorylation assays, alkaline phosphatase/CK2 inhibitor manipulation, and patch-clamp in CHO cells and native MNTB/brainstem neurons

    PMID:11160386 PMID:16136041

    Open questions at the time
    • Phosphatases mediating dephosphorylation not fully identified
    • Spatial control of kinase access not resolved
  5. 2011 High

    Mapping splice-isoform-specific axonal versus somatodendritic targeting clarified how identical biophysics yield compartment-specific control of firing.

    Evidence Isoform-specific immunohistochemistry/EM and terminal mutagenesis with patch-clamp in cultured neurons

    PMID:12091563 PMID:22105078

    Open questions at the time
    • Trafficking machinery recognizing the motif not identified
    • In vivo consequences of mistargeting not tested
  6. 2020 High

    Defining selectivity-filter and pore determinants of conduction and U-type inactivation linked specific residues to permeation and gating mechanisms.

    Evidence Site-directed mutagenesis (P-region, S6, T400) with single-channel and whole-cell patch-clamp and ionic manipulation

    PMID:16792699 PMID:32365329 PMID:7696467

    Open questions at the time
    • Physiological role of U-type inactivation in vivo unresolved
    • Glycosylation's in vivo contribution not established
  7. 2014 High

    Discovery that p.R320H causes MEAK via dominant-negative loss of function defined the first disease mechanism and a basis for fever-dependent clinical fluctuation.

    Evidence Exome sequencing plus heterologous patch-clamp, with temperature-dependent analysis and interneuron expression

    PMID:25401298 PMID:28380698 PMID:33735526

    Open questions at the time
    • Why interneuron viability/neurite development is affected not fully mechanistic
    • Therapeutic correction of dominant-negative effect not established
  8. 2019 High

    Functional characterization of additional variants expanded the disease spectrum, distinguishing simple loss of function, trafficking defects, and gain of function.

    Evidence Two-electrode voltage clamp in oocytes, mammalian patch-clamp, surface biotinylation, and a knockin mouse model across multiple variants

    PMID:31353855 PMID:36419348 PMID:37203213 PMID:41705663

    Open questions at the time
    • Genotype-phenotype prediction for novel variants incomplete
    • Gain-of-function variants studied in single reports with limited replication
  9. 2021 High

    Identifying a variant (A513V) that abolishes PKC modulation without altering basal current showed that disrupting regulatory tuning, not channel function, can be pathologically relevant.

    Evidence Phosphorylation assays and whole-cell patch-clamp in transfected cells

    PMID:34232791

    Open questions at the time
    • In vivo phenotype of regulatory loss not established
    • Whether this defines a distinct clinical class unknown
  10. 2022 High

    Cryo-EM structures provided the atomic framework for gating and modulation, localizing a rotated zinc-containing T1 domain and a voltage-sensor–pore modulator site coinciding with disease mutations.

    Evidence Cryo-EM of apo and ligand-bound human Kv3.1 with MD simulations, mutagenesis and electrophysiology

    PMID:35840580 PMID:36741467 PMID:37812700

    Open questions at the time
    • Structures of heteromeric Kv3.1/Kv3.2/Kv3.4 channels not determined
    • Structural basis of phosphoregulation not resolved
  11. 2024 High

    Establishing UBR5-driven ubiquitin-proteasomal degradation and trafficking control of Kv3.1 defined post-translational regulation of channel abundance relevant to inflammatory pain.

    Evidence Co-IP, ubiquitination assays, competitive peptide rescue, knockdown/knockout, and patch-clamp in spinal cord; oxidative-stress trafficking studies

    PMID:38725150 PMID:38865078

    Open questions at the time
    • Trafficking findings under oxidative stress are single-lab and lack in vivo validation
    • Other E3 ligases or deubiquitinases not characterized
  12. 2025 High

    Defining Kv3.1 as a downstream effector of the WNK1-OSR1/SPAK osmosensing cascade extended its role beyond fast firing to systemic homeostasis (vasopressin release).

    Evidence Conditional Osr1/Spak and Kv3.1 knockout in mouse OVLT with slice electrophysiology and AVP/urine measurements; p11-dependent regulation in PV cells

    PMID:32331822 PMID:41246868

    Open questions at the time
    • Direct biochemical coupling between SPAK/OSR1 and Kv3.1 not resolved
    • Generality of kinase-cascade regulation across neuron types unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse modulatory inputs (phosphorylation, splice targeting, auxiliary subunits, degradation, and kinase cascades) are integrated within native heteromeric channels in vivo, and how this can be therapeutically corrected in disease, remains unresolved.
  • No structure of native heteromers
  • Integrated in vivo regulatory model lacking
  • Pharmacological correction of dominant-negative and gain-of-function variants unestablished

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
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1643685 Disease 4
Partners
CLDN11KCNC2KCNC4KCNE3S100A10UBR5
Complex memberships
Kv3.1/Kv3.2 heteromeric channelKv3.1/Kv3.4 heteromeric channel

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Kv3.1 channel in mouse MNTB auditory neurons mediates a high-threshold, DTX-insensitive, TEA-sensitive (1 mM) rapidly activating and deactivating potassium current (IHT) that is required for neurons to follow high-frequency (>200 Hz) stimulation; pharmacological block and computer simulation confirmed this role. Patch-clamp voltage clamp in MNTB neurons, pharmacology (TEA, DTX), in situ hybridization, computer simulation with Kv3.1 kinetics The Journal of physiology High 9547392
1992 Kv3.1 encodes the type l (lymphocyte) voltage-gated K+ channel when expressed in Xenopus oocytes, with properties matching the native l-type channel in T lymphocytes; the gene maps to human chromosome 11. Heterologous expression in Xenopus oocytes, electrophysiology, RT-PCR in T cells The Journal of biological chemistry High 1400413
2005 The Kv3.1b splice variant is regulated by PKC phosphorylation in auditory brainstem neurons: in a quiet environment Kv3.1b is basally phosphorylated, high-frequency auditory or synaptic stimulation causes rapid dephosphorylation, which increases Kv3.1 current amplitude and facilitates high-frequency spiking. Immunochemical phosphorylation assay in rat brainstem neurons, computational modeling, patch-clamp recordings Nature neuroscience High 16136041
2001 Casein kinase 2 (CK2) constitutively phosphorylates Kv3.1, setting its high voltage-threshold of activation; dephosphorylation with alkaline phosphatase shifts activation >20 mV toward more negative potentials and increases whole-cell conductance, an effect mimicked by CK2 inhibitors but not PKC inhibitors. Patch-clamp whole-cell recording in CK2-inhibitor-treated CHO cells stably expressing Kv3.1 and native MNTB neurons; alkaline phosphatase application; biochemical phosphorylation assay The Journal of neuroscience High 11160386
2003 A splice variant of Kv3.4 coassembles with Kv3.1 subunits in rat brain fast-spiking neurons; this heterotetrameric assembly enhances spike repolarizing efficiency compared to Kv3.1 homomers, reducing spike duration and enabling higher repetitive firing rates. Molecular (RT-PCR), electrophysiological, and pharmacological co-expression studies in heterologous systems; co-assembly inferred from native neuron recordings Nature neuroscience High 12592408
2003 MiRP2 (MinK-related peptide 2) co-immunoprecipitates with Kv3.1b from rat brain membranes, forming a native complex; MiRP2 reduces Kv3.1b current density and slows activation kinetics. Native co-immunoprecipitation from rat brain membranes, heterologous co-expression, whole-cell patch-clamp, RNAi knockdown in PC12 cells and hippocampal neurons The Journal of neuroscience High 12954870
2002 The two alternatively spliced Kv3.1 isoforms (Kv3.1a and Kv3.1b) have distinct subcellular localizations in neurons: Kv3.1b is targeted to somatodendritic and axonal membranes, while Kv3.1a is targeted predominantly to axonal membranes with little somatic expression; this differential targeting is conferred by their distinct C-terminal splice domains. Immunohistochemistry with isoform-specific antibodies in mouse brain sections; electron microscopy Journal of neurophysiology High 12091563
2011 Alternative splicing controls polarized axonal targeting of Kv3.1: the Kv3.1b C-terminal splice domain creates electrostatic repulsion between N/C termini that unmasks an axonal targeting motif, directing Kv3.1b to axons; axonal Kv3.1b (but not dendritic Kv3.1a, despite identical biophysics) increases maximal firing frequency of hippocampal neurons. Mutagenesis of Kv3.1 termini, expression in cultured hippocampal neurons, patch-clamp recordings, local channel blocker application, computer simulation The Journal of biological chemistry High 22105078
2022 Cryo-EM structure of human Kv3.1a channel reveals a unique T1 cytoplasmic tetramerization domain arrangement that interacts with the C-terminal axonal targeting motif and gating machinery; S1/S2 linker-turret interactions stabilize voltage sensor-pore domain interface; S4/S5 linker residues influence gating kinetics; an electrostatic interaction between acidic residues in T1 α6 helix and R449 in S6T helices controls gating. Cryo-EM structure determination, molecular dynamics simulations, electrophysiology, mutagenesis Nature communications High 35840580
2022 Cryo-EM structure of human Kv3.1 at 2.6 Å reveals a T1 domain with a well-resolved Zinc site rotated 35° relative to other Kv channels; a positive modulator (Lu AG00563) binds at a novel site between the voltage-sensor domain and channel pore, a region that is a hotspot for disease-causing mutations. Cryo-EM structure determination of apo and ligand-bound Kv3.1 PNAS nexus High 36741467
1994 The P-region (S5-S6 loop) and C-terminal S6 segment both contribute to ion conduction: L401V in the P-region did not alter single-channel conductance or substantially change TEA sensitivity; M430L in S6 produced permeant-ion- and voltage-dependent channel flicker, indicating S6 contributes to the K+ conduction pathway. Site-directed mutagenesis, single-channel patch-clamp recordings in Xenopus oocytes Biophysical journal High 7696467
2006 N-glycosylation at positions N220 and N229 in the extracellular S1-S2 linker of Kv3.1 influences channel gating: double mutation N220Q/N229Q produced slower activation and a slight positive shift in voltage dependence without preventing plasma membrane trafficking; glycosylation sites were confirmed by PNGase F digestion and tunicamycin treatment. Site-directed mutagenesis (N220Q, N229Q), PNGase F and endoglycosidase H digestion, tunicamycin treatment, whole-cell patch-clamp, membrane fractionation in Sf9 cells The FEBS journal High 16792699
2014 The recurrent de novo KCNC1 p.Arg320His mutation causes progressive myoclonus epilepsy (PME/MEAK) through a dominant-negative loss-of-function effect on the Kv3.1 channel, reducing current amplitude when co-expressed with wild-type. Exome sequencing, functional analysis of mutant channel in heterologous expression system, whole-cell patch-clamp Nature genetics High 25401298
2017 The KCNC1 p.R320H mutant Kv3.1 channel causes dominant-negative loss of function by slowing channel activation; at elevated temperatures, wild-type Kv3.1 shows a leftward shift in activation, which could partially compensate for the mutant's loss of function—explaining transient clinical improvement with fever. Whole-cell patch-clamp of wild-type and R320H mutant channels at normal and elevated temperatures Annals of neurology High 28380698
2021 The Kv3.1b R320H variant (MEAK mutation) in cortical interneurons causes dominant-negative loss of function (slowing activation) and profoundly reduces excitability with inability to support high-frequency firing; additionally impairs neurite development and interneuron viability. No gating pore currents were introduced by R320H. Expression in cortical interneurons in vitro, patch-clamp, morphological analysis; oocyte recordings Epilepsia High 33735526
2019 KCNC1 variants beyond p.R320H cause developmental epileptic encephalopathy; p.Ala421Val causes loss of function through reduced whole-cell current without dominant-negative effect; other DEE-associated variants also produce loss of function with reduced whole-cell currents. Xenopus oocyte expression, automated two-electrode voltage clamp Annals of clinical and translational neurology High 31353855
2022 Three de novo KCNC1 variants in the S6 pore region cause gain of K+ channel function via prominent leftward (hyperpolarized) shift in voltage dependence of activation and slowed deactivation; this gain of function is predicted to reduce excitability of Kv3-expressing high-frequency-firing neurons. Whole-cell voltage clamp electrophysiology of variants in mammalian heterologous expression system Annals of clinical and translational neurology Medium 36419348
2021 The KCNC1 A513V mutation in the cytoplasmic C-terminus produces a channel that is functionally indistinguishable from wild-type in terms of current amplitude but is completely insensitive to PKC-mediated phosphorylation at the nearby S503 site, indicating loss of modulatory regulation rather than loss of channel function. Biochemical phosphorylation assays and whole-cell patch-clamp electrophysiology in transfected cells Journal of neurophysiology High 34232791
2023 A novel gain-of-function KCNC1 variant V425M produces larger currents, hyperpolarizing shift in activation gating, failure to inactivate, and slower kinetics; fluoxetine blocks both wild-type and V425M channels and produced clinical improvement in the affected patient. Patch-clamp recordings in transfected CHO cells, clinical pharmacology Epilepsia Medium 37203213
1999 Kv3.1 and Kv3.2 proteins co-immunoprecipitate from pallidal membrane extracts, indicating they form heteromeric channels in parvalbumin-containing globus pallidus neurons; the native Kv3 current in these neurons matches the electrophysiological properties of expressed Kv3.1/Kv3.2. Co-immunoprecipitation from native pallidal membranes, immunohistochemistry, patch-clamp of dissociated neurons Journal of neurophysiology High 10482766
2006 Kv3.1 associates with OSP/claudin-11 in oligodendrocytes; this interaction was identified by yeast two-hybrid and confirmed by co-immunoprecipitation; Kv3.1 accounts for ~50–75% of sustained K+ current in oligodendrocyte precursor cells (OPCs) and is required for OPC proliferation, migration, and axon myelination. Yeast two-hybrid, co-immunoprecipitation, antibody blockade, Kv3.1 knockout mice, functional assays (proliferation, migration, myelination) American journal of physiology. Cell physiology High 16624990
2003 Loss of both Kv3.1 and Kv3.3 in cerebellar granule cells causes broader parallel fiber action potentials and reduces paired-pulse facilitation at parallel fiber-Purkinje cell synapses; normal PPF can be restored by lowering extracellular Ca2+, indicating Kv3.1/Kv3.3 channels limit activity-dependent presynaptic Ca2+ influx. Kv3.1/Kv3.3 double-knockout mice, electrophysiological recordings of parallel fiber APs and synaptic transmission, extracellular Ca2+ manipulation The Journal of neuroscience High 12930807
2009 Kv3.1 in deep cerebellar nucleus (DCN) neurons is required for fast action potential repolarization and normal gait patterning; loss of Kcnc1 alleles in Kcnc3-null mice causes progressive spike broadening and deceleration in DCN neurons and increasing gait ataxia; Purkinje-cell-restricted Kv3.3 restoration failed to rescue gait ataxia when all Kcnc1 alleles were also absent. Genetic epistasis using Kcnc1/Kcnc3 allele combinations in mice; electrophysiological recordings of DCN neurons; behavioral analysis The Journal of neuroscience High 20016089
1998 Kv3.1 channel localizes to spine-like protrusions adjacent to postsynaptic membranes of cochlear nucleus bushy cells; K+ depletion within these confined spine-like structures produces apparent channel inactivation, demonstrating that compartmentalized ionic transients can be generated in spine-like structures. Electron immunomicroscopy, cell-attached patch-clamp of Kv3.1-transfected CHO cell vesicles mimicking spine geometry Proceedings of the National Academy of Sciences High 9465111
1998 Depolarization and calcium influx selectively increase Kv3.1 mRNA and high-threshold noninactivating K+ current in developing inferior colliculus neurons, an effect blocked by calcium channel blockers; increased Kv3.1-like current causes more rapid and complete action potential repolarization. Potassium-induced depolarization of inferior colliculus neurons, RT-PCR, voltage-clamp, calcium channel blockers, computer simulation The Journal of neuroscience High 9786983
2011 In deep cerebellar nuclear neurons, Kv3.1 channels dominate spike repolarization and enable fast evoked firing; in contrast, BK channels predominantly control spontaneous firing rate; when Kv3.1 is blocked, BK channels gain a compensatory role in repolarization. Whole-cell patch-clamp in DCN neurons with selective BK and Kv3.1 channel blockers (iberiotoxin, 4-aminopyridine 20 µM) Cerebellum Medium 21750937
1998 Heterologous expression of Kv3.1 in Aplysia bag cell neurons eliminates frequency-dependent spike broadening by rapid repolarization; this prevents the depolarizing afterpotential that would otherwise trigger prolonged spontaneous firing, demonstrating that spike broadening regulates calcium entry (up to 5-fold increase) which in turn induces long-term changes in excitability. Heterologous Kv3.1 expression in Aplysia neurons, current-clamp recordings, calcium current integral measurements, BAPTA chelation The Journal of neuroscience High 9801357
2020 U-type inactivation in Kv3.1 requires the second threonine (T400) of the selectivity filter TTVGYG sequence; T400A mutation eliminates U-type inactivation, yielding noninactivating currents, indicating the selectivity filter is allosterically involved in the inactivation gating mechanism. Site-directed mutagenesis (T400A), whole-cell patch-clamp in hKv3.1 expressed in heterologous cells, variation of extracellular K+ concentration Biophysical journal High 32365329
2013 The polyether toxin gambierol inhibits Kv3.1 by anchoring the voltage-sensing domain (VSD) in the resting/closed state; it acts via a lipid-exposed binding site outside the K+ permeation pathway; the resting channel conformation is the high-affinity state; strong depolarizations allow VSD movement to an activated-not-open state but toxin must dissociate before channel opens; a tetrameric concatemer with only one high-affinity site retains high toxin sensitivity. Gating current analysis, ionic current analysis, concatemer mutagenesis, whole-cell patch-clamp in heterologous cells The Journal of general physiology High 23401573
2024 UBR5 E3 ubiquitin ligase directly binds Kv3.1 and drives its ubiquitin-mediated proteasomal degradation in the spinal cord during inflammatory pain; Kv3.1 protein (but not mRNA) is decreased after CFA injection; a competitive peptide (TP-CH-401) matching the Kv3.1 ubiquitination motif rescues Kv3.1 expression and Kv currents and attenuates pain behaviors. Co-immunoprecipitation of UBR5-Kv3.1, ubiquitination assays, Kv3.1 KD/KO, intrathecal peptide injection, whole-cell patch-clamp Molecular neurobiology High 38865078
2025 In OVLT neurons, hypertonicity activates the WNK1→OSR1/SPAK kinase cascade, which in turn increases Kv3.1 channel currents to enhance action potential firing and trigger arginine vasopressin (AVP) release; deletion of Osr1 and Spak in the OVLT blunts hypertonicity-induced AP firing and AVP release, phenocopying Kv3.1 OVLT deletion. Conditional knockout of Osr1/Spak and Kv3.1 in mouse OVLT, brain slice electrophysiology, urine/AVP measurements, phosphorylation analysis FASEB journal High 41246868
1998 bFGF upregulates both Kv3.1a and Kv3.1b mRNA in cerebellar slices via PKC activation; combined bFGF and depolarization selectively increases Kv3.1b but not Kv3.1a; PKC inhibitors block bFGF-induced Kv3.1a increase; depolarization blocks nuclear PKC activation by bFGF, indicating differential signaling pathways regulate the two splice variants. In vitro cerebellar slices, RNase protection assays, PKC activity measurement, pharmacological inhibition The Journal of neuroscience Medium 9526005
1999 Cell-type specific expression of Kv3.1 is conferred by a negatively acting regulatory element in the 5' UTR (+350 to +158) that represses expression in non-neuronal cells; a weak positive enhancer in the proximal promoter (-123 to -71) also contributes; the 5' UTR element can confer specificity to a heterologous (thymidine kinase) promoter. Deletion analysis of Kv3.1 promoter in cell lines and transgenic mice, transient transfection assays Journal of neurochemistry Medium 10501178
2024 The KCNC1 variant p.A421V causes loss of function by reducing Kv3.1 cell surface expression in PV-INs; in a mouse knockin model (Kcnc1-A421V/+), PV-IN current density is decreased, intrinsic excitability is profoundly impaired, inhibitory neurotransmission is altered in young adults, and animals develop myoclonic seizures and premature lethality. Transgenic knockin mouse model, immunohistochemistry, outside-out nucleated macropatch recordings, current-clamp electrophysiology, in vivo two-photon Ca2+ imaging, EEG eLife High 41705663
2020 p11 regulates the subcellular localization and cellular level of Kv3.1 in parvalbumin interneurons; deletion of p11 from PV cells reduces hippocampal Kv3.1 levels and attenuates high-frequency firing capacity; upregulation or pharmacological activation of Kv3.1 in dentate gyrus PV cells induces resilience to depression. Conditional p11 deletion in PV cells, electrophysiology, imaging, biochemical studies, viral-mediated Kv3.1 upregulation, Kv3.1 agonist application Biological psychiatry High 32331822
2024 Oxidative stress-induced reduction in Kv3.1 current density is caused by reduced trafficking to the cell surface associated with Src phosphorylation and ER stress, not by direct oxidation of the channel protein or reduced transcript/total protein levels; melatonin reverses this effect. D-galactose oxidative stress cell model, patch-clamp, Src phosphorylation analysis, ER stress markers, surface biotinylation Aging cell Medium 38725150
2008 Fluoxetine acts as an open-channel blocker of Kv3.1: inhibition is voltage-dependent over the channel opening range, accelerates current decay, slows deactivation (tail crossover), and is use-dependent, with IC50 ~13.4 µM. Whole-cell patch-clamp on CHO cells stably expressing rat Kv3.1 Journal of pharmacological sciences Medium 18187934
2001 Norfluoxetine (major fluoxetine metabolite) acts as an open-channel blocker of Kv3.1 with IC50 ~0.80 µM (whole-cell) and 0.19 µM (inside-out, cytoplasmic application); both drugs inhibit Kv3.1 at clinically relevant concentrations. Whole-cell and inside-out patch-clamp on CHO cells expressing rat Kv3.1 Neuropharmacology Medium 11543764
2023 Cryo-EM structure of Kv3.1 with a novel positive modulator reveals the compound binding site and structural basis for positive modulation; structural analysis defines molecular determinants at the voltage sensor-pore interface. Cryo-EM structure determination of Kv3.1 in complex with positive modulator, biophysical characterization Proceedings of the National Academy of Sciences High 37812700
2024 The KCNC1 S474C variant causes retention of Kv3.1 in the endoplasmic reticulum and failure of ER-to-Golgi trafficking, reducing channel presence at the plasma membrane; neurons expressing Kv3.1-S474C show reduced firing frequency and exclusion from the axon initial segment. Electrophysiological and biochemical assays in transfected cells, immunofluorescence in murine primary cultures, computational neuronal modeling bioRxivpreprint Medium

Source papers

Stage 0 corpus · 87 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Contribution of the Kv3.1 potassium channel to high-frequency firing in mouse auditory neurones. The Journal of physiology 284 9547392
2014 A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. Nature genetics 239 25401298
1992 Expression of the mRNAs for the Kv3.1 potassium channel gene in the adult and developing rat brain. Journal of neurophysiology 199 1432046
2003 Kv3.4 subunits enhance the repolarizing efficiency of Kv3.1 channels in fast-spiking neurons. Nature neuroscience 118 12592408
1997 Differential expression of K4-AP currents and Kv3.1 potassium channel transcripts in cortical neurons that develop distinct firing phenotypes. The Journal of neuroscience : the official journal of the Society for Neuroscience 117 9096148
2005 Acoustic environment determines phosphorylation state of the Kv3.1 potassium channel in auditory neurons. Nature neuroscience 107 16136041
1999 Delayed rectifier currents in rat globus pallidus neurons are attributable to Kv2.1 and Kv3.1/3.2 K(+) channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 97 10414968
1994 GABA-ergic interneurons of the striatum express the Shaw-like potassium channel Kv3.1. Synapse (New York, N.Y.) 84 7825124
1999 Kv3.1-Kv3.2 channels underlie a high-voltage-activating component of the delayed rectifier K+ current in projecting neurons from the globus pallidus. Journal of neurophysiology 83 10482766
1998 When, where, and how much? Expression of the Kv3.1 potassium channel in high-frequency firing neurons. Journal of neurobiology 81 9777733
2004 Loss of Kv3.1 tonotopicity and alterations in cAMP response element-binding protein signaling in central auditory neurons of hearing impaired mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 80 14985434
2002 Differential subcellular localization of the two alternatively spliced isoforms of the Kv3.1 potassium channel subunit in brain. Journal of neurophysiology 76 12091563
2003 MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels in mammalian brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 75 12954870
1992 The Shaw-related potassium channel gene, Kv3.1, on human chromosome 11, encodes the type l K+ channel in T cells. The Journal of biological chemistry 75 1400413
2004 Activity-dependent regulation of the potassium channel subunits Kv1.1 and Kv3.1. The Journal of comparative neurology 74 14755528
2013 Kv3.1-containing K(+) channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs. Molecular psychiatry 69 23628987
2003 Motor dysfunction and altered synaptic transmission at the parallel fiber-Purkinje cell synapse in mice lacking potassium channels Kv3.1 and Kv3.3. The Journal of neuroscience : the official journal of the Society for Neuroscience 68 12930807
2001 Expression of the Kv3.1 potassium channel in the avian auditory brainstem. The Journal of neuroscience : the official journal of the Society for Neuroscience 67 11160428
1998 Depolarization selectively increases the expression of the Kv3.1 potassium channel in developing inferior colliculus neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 9786983
2004 Allele-dependent changes of olivocerebellar circuit properties in the absence of the voltage-gated potassium channels Kv3.1 and Kv3.3. The European journal of neuroscience 60 15217387
2017 Myoclonus epilepsy and ataxia due to KCNC1 mutation: Analysis of 20 cases and K+ channel properties. Annals of neurology 59 28380698
2006 Selective blockage of Kv1.3 and Kv3.1 channels increases neural progenitor cell proliferation. Journal of neurochemistry 54 17029597
2001 Properties of interneurones in the intermediolateral cell column of the rat spinal cord: role of the potassium channel subunit Kv3.1. Neuroscience 52 11566512
2001 Casein kinase 2 determines the voltage dependence of the Kv3.1 channel in auditory neurons and transfected cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 48 11160386
2008 Open channel block of Kv3.1 currents by fluoxetine. Journal of pharmacological sciences 44 18187934
1994 The P-region and S6 of Kv3.1 contribute to the formation of the ion conduction pathway. Biophysical journal 44 7696467
2019 Encephalopathies with KCNC1 variants: genotype-phenotype-functional correlations. Annals of clinical and translational neurology 43 31353855
2001 Effects of norfluoxetine, the major metabolite of fluoxetine, on the cloned neuronal potassium channel Kv3.1. Neuropharmacology 42 11543764
1998 The expression of two splice variants of the Kv3.1 potassium channel gene is regulated by different signaling pathways. The Journal of neuroscience : the official journal of the Society for Neuroscience 42 9526005
2011 Alternative splicing regulates kv3.1 polarized targeting to adjust maximal spiking frequency. The Journal of biological chemistry 37 22105078
2006 K+ channel KV3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development. American journal of physiology. Cell physiology 37 16624990
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 37 8020965
1993 Localization of a highly conserved human potassium channel gene (NGK2-KV4; KCNC1) to chromosome 11p15. Genomics 37 8449507
2020 Reduced Kv3.1 Activity in Dentate Gyrus Parvalbumin Cells Induces Vulnerability to Depression. Biological psychiatry 35 32331822
2002 Resilient RTN fast spiking in Kv3.1 null mice suggests redundancy in the action potential repolarization mechanism. Journal of neurophysiology 35 11877504
1999 Expression of Kv3.1 and Kv4.2 genes in developing cerebellar granule cells. Developmental neuroscience 34 10449980
2018 Kv3.1 and Kv3.4, Are Involved in Cancer Cell Migration and Invasion. International journal of molecular sciences 33 29614836
2016 Myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK) is caused by heterozygous KCNC1 mutations. Epileptic disorders : international epilepsy journal with videotape 33 27629860
2009 Rescue of motor coordination by Purkinje cell-targeted restoration of Kv3.3 channels in Kcnc3-null mice requires Kcnc1. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 20016089
2006 Characterization of N-glycosylation consensus sequences in the Kv3.1 channel. The FEBS journal 32 16792699
2017 Loss of Function of KCNC1 is associated with intellectual disability without seizures. European journal of human genetics : EJHG 30 28145425
2005 Inhibition of the cloned delayed rectifier K+ channels, Kv1.5 and Kv3.1, by riluzole. Neuroscience 29 15964489
2003 Localization of KCNC1 (Kv3.1) potassium channel subunits in the avian auditory nucleus magnocellularis and nucleus laminaris during development. Journal of neurobiology 29 12672015
1998 Activation of Kv3.1 channels in neuronal spine-like structures may induce local potassium ion depletion. Proceedings of the National Academy of Sciences of the United States of America 29 9465111
2017 Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage. Scientific reports 27 29235497
2000 Sustained upregulation in embryonic spinal neurons of a Kv3.1 potassium channel gene encoding a delayed rectifier current. Journal of neurobiology 26 10645974
2022 Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain. Nature communications 25 35840580
2020 Kv3.1 and Kv3.3 subunits differentially contribute to Kv3 channels and action potential repolarization in principal neurons of the auditory brainstem. The Journal of physiology 25 32246836
2009 Experimental and simulation studies on the mechanisms of levetiracetam-mediated inhibition of delayed-rectifier potassium current (KV3.1): contribution to the firing of action potentials. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 22 20065495
2007 Open channel block of A-type, kv4.3, and delayed rectifier K+ channels, Kv1.3 and Kv3.1, by sibutramine. The Journal of pharmacology and experimental therapeutics 22 17312186
2013 The ladder-shaped polyether toxin gambierol anchors the gating machinery of Kv3.1 channels in the resting state. The Journal of general physiology 21 23401573
2011 BK and Kv3.1 potassium channels control different aspects of deep cerebellar nuclear neurons action potentials and spiking activity. Cerebellum (London, England) 20 21750937
1998 Heterologous expression of the Kv3.1 potassium channel eliminates spike broadening and the induction of a depolarizing afterpotential in the peptidergic bag cell neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 20 9801357
2015 Biophysical characterization of KV3.1 potassium channel activating compounds. European journal of pharmacology 17 25845309
2005 Age-related changes in the distribution of Kv1.1 and Kv3.1 in rat cochlear nuclei. Neurological research 17 15949244
2004 Maturation of spiking activity in trout retinal ganglion cells coincides with upregulation of Kv3.1- and BK-related potassium channels. Journal of neuroscience research 17 14689447
2023 A novel KCNC1 gain-of-function variant causing developmental and epileptic encephalopathy: "Precision medicine" approach with fluoxetine. Epilepsia 16 37203213
2022 A KCNC1-related neurological disorder due to gain of Kv3.1 function. Annals of clinical and translational neurology 16 36419348
2022 Apo and ligand-bound high resolution Cryo-EM structures of the human Kv3.1 channel reveal a novel binding site for positive modulators. PNAS nexus 16 36741467
2021 Kv3.1 channelopathy: a novel loss-of-function variant and the mechanistic basis of its clinical phenotypes. Annals of translational medicine 16 34733949
2018 Effects of AUT00063, a Kv3.1 channel modulator, on noise-induced hyperactivity in the dorsal cochlear nucleus. Hearing research 15 29453003
2013 Kv3.1 channels stimulate adult neural precursor cell proliferation and neuronal differentiation. The Journal of physiology 15 23478135
2018 Familial cases of progressive myoclonic epilepsy caused by maternal somatic mosaicism of a recurrent KCNC1 p.Arg320His mutation. Brain & development 14 29428275
2017 Antidepressant drug paroxetine blocks the open pore of Kv3.1 potassium channel. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 14 29302214
1999 Cell type-specific expression of the Kv3.1 gene is mediated by a negative element in the 5' untranslated region of the Kv3.1 promoter. Journal of neurochemistry 14 10501178
2020 Progressive myoclonic epilepsy: myoclonic epilepsy and ataxia due to KCNC1 mutation (MEAK): a case report and review of the literature. Epileptic disorders : international epilepsy journal with videotape 13 32972906
2001 Expression of a voltage-dependent potassium channel protein (Kv3.1) in the embryonic development of the auditory system. Journal of neuroscience research 13 11433426
2023 Identification, structural, and biophysical characterization of a positive modulator of human Kv3.1 channels. Proceedings of the National Academy of Sciences of the United States of America 12 37812700
2021 Progressive myoclonus epilepsy KCNC1 variant causes a developmental dendritopathy. Epilepsia 12 33735526
2005 Aminoglycosides block the Kv3.1 potassium channel and reduce the ability of inferior colliculus neurons to fire at high frequencies. Journal of neurobiology 11 15547932
2003 Biophysical properties of Kv3.1 channels in SH-SY5Y human neuroblastoma cells. Receptors & channels 11 14698966
2021 A KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation. Journal of neurophysiology 10 34232791
2021 Social impairments in mice lacking the voltage-gated potassium channel Kv3.1. Behavioural brain research 8 34274375
2020 The Selectivity Filter Is Involved in the U-Type Inactivation Process of Kv2.1 and Kv3.1 Channels. Biophysical journal 8 32365329
2001 Developmental expression of a voltage-dependent potassium channel (Kv3.1) in auditory neurons without cochlear input. Journal of neuroscience research 7 11438981
2024 Oxidative stress-related cellular aging causes dysfunction of the Kv3.1/KCNC1 channel reverted by melatonin. Aging cell 6 38725150
2009 Effect of psoralen on the cloned Kv3.1 currents. Archives of pharmacal research 6 19387585
2020 Generation of induced pluripotent stem cell GZHMCi001-A and GZHMCi001-B derived from peripheral blood mononuclear cells of epileptic patients with KCNC1 mutation. Stem cell research 5 32712483
2023 Kv3.1 Voltage-gated Potassium Channels Modulate Anxiety-like Behaviors in Female Mice. Neuroscience 4 38157976
2024 Kv3.1 Interaction with UBR5 Is Required for Chronic Inflammatory Pain. Molecular neurobiology 1 38865078
2023 Effects of rosiglitazone, an antidiabetic drug, on Kv3.1 channels. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 1 36575937
2026 A novel de Novo KCNC1 mutation (c.1147 C > T) presenting with epilepsy and ADHD: a case report and literature review. BMC neurology 0 41622135
2026 Impaired excitability of fast-spiking neurons in a novel mouse model of KCNC1 epileptic encephalopathy. eLife 0 41705663
2025 KCNC1-Related Progressive Myoclonus Epilepsy: A Case Report. Clinical case reports 0 40765656
2025 Central Osmolality Sensing for Arginine Vasopressin Release Is Mediated by WNK1-OSR1/SPAK-Kv3.1 Cascade. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41246868
2024 Impaired excitability of fast-spiking neurons in a novel mouse model of KCNC1 epileptic encephalopathy. bioRxiv : the preprint server for biology 0 39386579
2013 Evolutionary conservation of Kv3.1 in the barn owl Tyto alba. Brain, behavior and evolution 0 23615168

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