Affinage

KCNC3

Voltage-gated potassium channel KCNC3 · UniProt Q14003

Length
757 aa
Mass
80.6 kDa
Annotated
2026-04-28
50 papers in source corpus 27 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNC3 encodes the voltage-gated potassium channel Kv3.3, a Shaw-family subunit that activates at depolarized potentials to mediate fast action potential repolarization in high-frequency-firing neurons, including cerebellar Purkinje cells, deep cerebellar nuclei neurons, and auditory brainstem neurons (PMID:18256249, PMID:32246836, PMID:35510987). The channel undergoes N-type inactivation via its N-terminal domain, regulated by PKC phosphorylation of Ser3 and Ser9, while the cytoplasmic C-terminus recruits Hax-1 and Arp2/3 to assemble a cortical actin network that prevents rapid inactivation during brief depolarizations (PMID:12923191, PMID:18539595, PMID:26997484). Kv3.3 also directly binds and stimulates TBK1 to control Hax-1 trafficking via multivesicular bodies, and is anchored at the Purkinje cell soma membrane through Ankyrin-R/β3-spectrin linkage (PMID:33741962, PMID:34785580). Dominant mutations in KCNC3 cause spinocerebellar ataxia type 13 (SCA13) through mechanisms including dominant-negative current suppression (R420H, R423H), shifted voltage dependence of activation (F448L, R423H), and disruption of the C-terminal actin/TBK1 signaling axis (G592R), leading to impaired high-frequency firing, elevated intracellular calcium, and Purkinje cell degeneration (PMID:16501573, PMID:19953606, PMID:24218544, PMID:32644043).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1992 High

    The genomic organization and chromosomal location of KCNC3 were established, revealing a split-exon architecture encoding the N-terminal and transmembrane domains separately on chromosome 19, providing the molecular foundation for subsequent functional studies.

    Evidence Genomic cloning, cDNA isolation, Southern blotting, and chromosomal mapping

    PMID:1740329

    Open questions at the time
    • No functional characterization of channel activity at this stage
    • Splice variant diversity not explored
  2. 2003 High

    The N-terminal domain was identified as the mediator of N-type inactivation, resolving how Kv3.3 can transition between sustained and inactivating modes; concurrently, Kv3.1/Kv3.3 double-knockout mice revealed that these subunits jointly control parallel fiber AP width and presynaptic calcium dynamics in the cerebellum.

    Evidence Start-codon and Kozak mutagenesis with electrophysiology in CHO/HEK cells; single and double KO mice with synaptic recordings

    PMID:12923191 PMID:12930807

    Open questions at the time
    • Molecular identity of inactivation ball peptide not resolved
    • Relative contribution of Kv3.3 vs Kv3.1 at individual synapses unclear
  3. 2004 High

    Kv3.3, not Kv3.1, was shown to be the essential subunit for Purkinje cell AP repolarization and olivocerebellar tremor generation, establishing subunit-specific non-redundant roles in the cerebellar circuit.

    Evidence Kv3.3 and Kv3.1 single and double KO mice with harmaline tremor assay and Purkinje cell electrophysiology

    PMID:15217387

    Open questions at the time
    • Mechanism of subunit-specific expression patterns in Purkinje cells unknown
    • Whether Kv3.3 homo- or heteromeric channels predominate in vivo unresolved
  4. 2005 Medium

    A C-terminal targeting domain containing a putative PDZ-binding motif was identified as directing Kv3.3 to distal dendrites, revealing that subcellular localization is encoded within the channel itself.

    Evidence In vivo viral expression with C-terminal deletion/retargeting in electrosensory lateral line lobe

    PMID:16354911

    Open questions at the time
    • Identity of the interacting PDZ-domain protein not determined
    • Relevance to mammalian dendritic targeting not confirmed
  5. 2006 High

    The first SCA13-causing mutations were functionally characterized, showing that R420H acts as a dominant-negative non-conducting subunit while F448L shifts activation negatively, establishing two distinct pathogenic mechanisms for the same disease locus.

    Evidence Xenopus oocyte expression with electrophysiology and co-expression of wild-type/mutant subunits

    PMID:16501573

    Open questions at the time
    • In vivo consequences of these mutations on Purkinje cell firing not yet tested
    • Whether heteromeric gating changes contribute to R420H pathogenesis unknown
  6. 2008 High

    PKC was shown to regulate N-type inactivation through phosphorylation of Ser3/Ser9, providing a signaling mechanism by which neuromodulators dynamically switch Kv3.3 between inactivating and sustained modes; simultaneously, Kv3.3 was proven essential for complex spike spikelet generation and motor coordination specifically within Purkinje cells via cell-type-specific rescue.

    Evidence Mutagenesis of Ser3/Ser9 with PKC pharmacology; Purkinje-cell-restricted transgenic rescue in Kcnc3 KO mice with electrophysiology and behavioral testing

    PMID:18256249 PMID:18448641 PMID:18539595

    Open questions at the time
    • Physiological conditions triggering PKC-mediated modulation in vivo unknown
    • Why motor learning was not rescued by Purkinje cell Kv3.3 restoration remains unexplained
  7. 2009 High

    Genetic epistasis between Kv3.3 in Purkinje cells and Kv3.1 in deep cerebellar nuclei demonstrated that fast repolarization at multiple nodes of the cerebellar circuit is required for normal motor coordination, establishing a circuit-level requirement beyond single cell types.

    Evidence Multi-allele Kcnc1/Kcnc3 crosses with Purkinje-cell transgenic rescue, DCN electrophysiology, and gait analysis

    PMID:20016089

    Open questions at the time
    • Specific Kv3 subunit composition in DCN neurons not defined
    • Contribution of mossy fiber inputs and other interneurons not addressed
  8. 2010 High

    Dendritic Kv3.3 channels were shown to oppose Ca²⁺ spike initiation in distal Purkinje cell dendrites, extending the functional role of Kv3.3 beyond somatic/axonal repolarization to include regulation of dendritic excitability and climbing fiber-evoked calcium signaling.

    Evidence Kv3.3 KO mice with voltage clamp, local pharmacology, and dendritic Ca²⁺ imaging

    PMID:20357073

    Open questions at the time
    • Molecular basis for dendritic vs somatic Kv3.3 targeting not resolved
    • Functional impact on synaptic plasticity at climbing fiber synapses not tested
  9. 2010 High

    R423H was distinguished from R420H by its dual mechanism: both dominant-negative suppression and altered heteromeric channel gating (hyperpolarized activation, slowed kinetics), explaining the more severe early-onset SCA13 phenotype with R423H.

    Evidence Xenopus oocyte electrophysiology with defined wild-type/mutant subunit ratios

    PMID:19953606 PMID:22289912

    Open questions at the time
    • Structural basis for why adjacent arginine mutations produce different gating effects unknown
    • In vivo confirmation of heteromeric gating shifts lacking
  10. 2013 Medium

    Mutant Kv3.3 (R424H) was shown to cause Purkinje cell death via calcium overload secondary to AP broadening, with rescue by P/Q-type calcium channel blockade, establishing a mechanistic link from channel dysfunction to neurodegeneration.

    Evidence Lentiviral expression of R424H in cultured Purkinje cells with electrophysiology, Ca²⁺ imaging, and pharmacological rescue

    PMID:24218544

    Open questions at the time
    • Whether P/Q-type blockade rescues degeneration in vivo untested
    • Contribution of non-cell-autonomous mechanisms not evaluated
  11. 2016 High

    The C-terminal proline-rich domain was identified as an Arp2/3/Hax-1 recruitment platform that builds a cortical actin network preventing N-type inactivation during brief depolarizations, revealing a non-canonical channel function in cytoskeletal organization.

    Evidence Co-IP, pulldown, in vitro actin assays, electrophysiology, and stem cell-derived neuron imaging; disease mutation disrupts Arp2/3 but not Hax-1 binding

    PMID:26997484

    Open questions at the time
    • Structural details of the proline-rich domain interaction with Hax-1 and Arp2/3 not resolved
    • Whether actin-dependent regulation operates in all Kv3.3-expressing neuron types unknown
  12. 2018 Medium

    A proline deletion (p.Pro583_Pro585del) in the C-terminal domain slowed inactivation and reduced actin-dependent regulation without impairing surface trafficking, providing finer dissection of how the proline-rich region controls gating through the actin cytoskeleton.

    Evidence Mammalian cell electrophysiology with latrunculin B pharmacology and immunofluorescence

    PMID:29949095

    Open questions at the time
    • Whether this variant is pathogenic in humans not established
    • Direct biophysical mechanism linking actin to inactivation gate not resolved
  13. 2020 High

    Cell-type-specific knockout studies in auditory brainstem demonstrated that LSO neurons absolutely require Kv3.3 for fast repolarization while MNTB neurons can substitute Kv3.1, establishing differential subunit dependence across auditory nuclei.

    Evidence Kv3.3 and Kv3.1 KO mice with patch-clamp, Ca²⁺ imaging, and TEA pharmacology in LSO and MNTB

    PMID:32246836

    Open questions at the time
    • Hearing phenotype in Kv3.3 KO mice not fully characterized
    • Whether Kv3.3 heteromerizes with Kv3.1 in these nuclei not determined
  14. 2021 High

    Kv3.3 was discovered to directly bind and activate TBK1, controlling Hax-1 trafficking through multivesicular bodies; the G592R SCA13 mutation hyperactivates TBK1, causing Hax-1 degradation, exosome release, and neuronal death—a non-conducting function distinct from ion permeation. ASO-mediated suppression of mutant Kv3.3 reversed TBK1 overactivation and rescued motor function in G592R mice.

    Evidence Reciprocal Co-IP, subcellular fractionation, cell death assays, mouse models; intracerebroventricular ASO with biochemical and rotarod endpoints

    PMID:33741962 PMID:34820911

    Open questions at the time
    • Structural basis of Kv3.3-TBK1 interaction not determined
    • Whether TBK1 activation contributes to other SCA13 mutations unknown
    • Long-term therapeutic window of ASO approach not defined
  15. 2021 High

    Ankyrin-R was identified as the cytoskeletal anchor linking Kv3.3 to β3 spectrin at the Purkinje cell soma; loss of AnkR reduced somatic Kv3.3 levels and caused ataxia and neurodegeneration, establishing a somatic retention mechanism complementary to the C-terminal dendritic targeting signal.

    Evidence Co-IP, conditional AnkR KO (Nestin-Cre and Pcp2-Cre), immunofluorescence, behavioral phenotyping

    PMID:34785580

    Open questions at the time
    • Binding interface between AnkR and Kv3.3 not mapped
    • Whether AnkR also anchors Kv3.3 outside the cerebellum unknown
  16. 2022 High

    Kv3.3 was shown to be the dominant presynaptic Kv3 subunit at the calyx of Held, where it constrains AP duration, limits neurotransmitter release, and supports faithful high-frequency transmission; a voltage-sensor mutation (G434V) separately confirmed that loss of Kv3.3 conductance impairs spatial learning.

    Evidence Kv3.3 KO mice with calyx electrophysiology and computational modeling; CRISPR G434V KI mice with behavioral testing

    PMID:35510987 PMID:35881790

    Open questions at the time
    • Whether Kv3.3 loss at the calyx affects auditory processing in behaving animals not tested
    • Cognitive circuits dependent on Kv3.3 beyond cerebellum and auditory brainstem not mapped
  17. 2024 Medium

    Translational regulation of Kv3.3 was demonstrated via a Kozak sequence variant that increases protein expression, and the E675K C-terminal variant was shown to reduce current and enhance cumulative inactivation that is antagonized by elevated extracellular potassium.

    Evidence Luciferase reporter/qPCR assays for Kozak variant; Xenopus oocyte voltage-clamp for E675K with extracellular K⁺ manipulation

    PMID:39416683 PMID:39596509

    Open questions at the time
    • In vivo relevance of Kozak variant to disease phenotype unresolved
    • Mechanism by which extracellular K⁺ antagonizes inactivation not clarified at structural level

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of the Kv3.3 C-terminal signaling complex (Hax-1/Arp2/3/TBK1), the identity of PDZ-domain proteins mediating dendritic targeting, whether non-conducting functions of Kv3.3 contribute to pathogenesis across all SCA13 mutations, and the full extent of Kv3.3-dependent circuits beyond the cerebellum and auditory brainstem.
  • No high-resolution structure of Kv3.3 or its signaling complexes
  • PDZ-domain targeting partner unidentified
  • Relative contribution of conducting vs non-conducting functions to SCA13 pathogenesis not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0008092 cytoskeletal protein binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 2
Pathway
R-HSA-112316 Neuronal System 8 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 2
Partners
ACTR2ANK1HAX1SPTBN2TBK1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 KCNC3 R420H mutation, located in the voltage-sensing domain, produces a non-functional channel subunit when expressed alone and exerts a dominant-negative effect when co-expressed with wild-type KCNC3 in Xenopus oocytes. KCNC3 F448L shifts the activation curve in the negative direction and slows channel closing. Xenopus oocyte heterologous expression with electrophysiology and co-expression experiments Nature genetics High 16501573
2003 Kv3.3 channels mediate N-type inactivation via an NH2-terminal domain; the rate and voltage dependence of inactivation differ significantly between cell expression systems (CHO vs HEK), with fast, voltage-dependent N-type inactivation requiring correct translation initiation from the first methionine start codon. Heterologous expression in CHO and HEK cells with mutagenesis of Kozak sequence and start codon The Journal of biological chemistry High 12923191
2008 Protein kinase C (PKC) modulates Kv3.3 by increasing current amplitude and removing N-type inactivation; PKC acts via phosphorylation of serines at positions 3 and 9 within the N-terminal domain (first 78 amino acids), as deletion of this domain abolishes inactivation and mutagenesis of these serines affects PKC modulation. Heterologous expression in mammalian cells and Xenopus oocytes; N-terminal deletion and serine mutagenesis; PKC activator/inhibitor pharmacology; computer simulations The Journal of biological chemistry High 18539595
2016 The cytoplasmic C-terminus of Kv3.3 contains a proline-rich domain that recruits Arp2/3 to the plasma membrane via binding to Hax-1, forming a stable cortical actin network resistant to cytochalasin D; this actin network is required to prevent rapid N-type inactivation during short depolarizations. A disease-causing mutation within this proline-rich domain impairs Arp2/3 recruitment but not Hax-1 binding. Co-immunoprecipitation, biochemical pulldown, in vitro actin assays, electrophysiology, stem cell-derived neuron imaging Cell High 26997484
2021 Kv3.3 channels directly bind and stimulate Tank Binding Kinase 1 (TBK1), which controls trafficking of membrane proteins into multivesicular bodies. TBK1 activity is required for Kv3.3 binding to its auxiliary subunit Hax-1. A disease-causing Kv3.3 mutation (G592R) greatly increases TBK1 stimulation, leading to Hax-1 degradation via multivesicular body/lysosomal trafficking, exosome release, caspase activation, and neuronal death. Co-immunoprecipitation, subcellular fractionation, biochemical assays, cell death assays, mouse model studies Nature communications High 33741962
2021 Ankyrin-R (AnkR) physically interacts with Kv3.3 and β3 spectrin, linking Kv3.3 to the spectrin-based cytoskeleton in Purkinje neurons; loss of AnkR reduces somatic membrane levels of Kv3.3 in Purkinje neurons and causes ataxia and progressive neurodegeneration. Co-immunoprecipitation, conditional knockout mice (Ank1 floxed × Nestin-Cre and Pcp2-Cre), immunofluorescence, western blot The Journal of neuroscience High 34785580
2008 Kv3.3 channels at the Purkinje cell soma are necessary for generation of repetitive spikelets in the complex spike; spikelet generation occurs at axosomatic membranes, not dendrites. Kv3 and resurgent Na+ channels are coordinated to limit Na+ channel inactivation and enable rapid repetitive firing. Acute slice electrophysiology in Kv3.3 knockout mice, dual somatic-dendritic recordings, local pharmacology, computational modeling The Journal of neuroscience High 18256249
2008 Purkinje-cell-restricted restoration of Kv3.3 in Kcnc3-null mice restores normal simple spike brevity and complex spike spikelets and rescues motor coordination (lateral deviation, beam slips), but not motor learning, demonstrating that Kv3.3 function in Purkinje cells is specifically required for motor coordination. Transgenic rescue (Purkinje-cell-targeted Kv3.3 re-expression), electrophysiology, behavioral assays in Kcnc3-null mice The Journal of neuroscience High 18448641
2009 Rescue of motor coordination by Purkinje-cell-restricted Kv3.3 restoration requires Kcnc1 in the deep cerebellar nuclei (DCN); loss of Kcnc1 alleles in addition to Kcnc3 produces spike broadening and deceleration in DCN neurons, establishing that fast repolarization in both Purkinje cells and DCN neurons is necessary for normal motor coordination and gait patterning. Genetic epistasis with multiple allele combinations, Purkinje-cell-restricted transgenic rescue, DCN electrophysiology, gait analysis The Journal of neuroscience High 20016089
2003 Combined loss of Kv3.1 and Kv3.3 in mice broadens parallel fiber action potentials, alters paired-pulse facilitation (PPF) at parallel fiber-Purkinje cell synapses in a gene-dose-dependent manner, increases activity-dependent presynaptic Ca2+ influx, and facilitates induction of metabotropic glutamate receptor-mediated EPSCs. Double and single knockout mice, electrophysiology (extracellular and intracellular recordings), Ca2+ manipulation, motor behavioral assays The Journal of neuroscience High 12930807
2004 Kv3.3 subunits are essential for the olivocerebellar system to generate harmaline-induced tremor; Kv3.3-single mutant mice lack harmaline tremor entirely and have approximately 100% broader Purkinje cell action potentials compared to wild-type or Kv3.1-single mutants. Kv3.3 and Kv3.1 single and double mutant mice, harmaline pharmacology, Purkinje cell electrophysiology, immunohistochemistry The European journal of neuroscience High 15217387
2010 Dendritic Kv3.3 channels in Purkinje cells oppose Ca2+ spike initiation and regulate propagation of electrical activity and Ca2+ influx in distal dendrites; Kv3.3 knockout mice show enhanced dendritic excitability and specifically elevated Ca2+ signals in distal dendrites following climbing fiber activation. Kv3.3 knockout mice, voltage clamp, local pharmacology, Ca2+ imaging throughout Purkinje cell dendritic tree Journal of neurophysiology High 20357073
2010 KCNC3 R423H mutation exhibits dominant-negative properties similar to R420H (nonfunctional subunit suppressing current amplitude); however, R423H additionally produces altered gating when co-assembled with wild-type subunits (hyperpolarized activation shift, slower activation, modestly slower deactivation), while R420H-containing channels retain near-wild-type gating, explaining why R423H causes early-onset disease. Xenopus oocyte heterologous expression, electrophysiology of heteromeric channels with varying wild-type/mutant subunit ratios Human mutation High 19953606 22289912
2005 A C-terminal domain of Kv3.3 directs channels to distal dendrites; the targeting domain includes a consensus sequence predicted to bind PDZ-type protein-protein interaction motifs, as demonstrated by retargeting experiments using in vivo viral injections in the electrosensory system. Immunohistochemistry, in vivo viral injection for recombinant channel expression, C-terminal domain deletion and retargeting experiments The Journal of neuroscience Medium 16354911
2014 KCNC3 R420H protein displays reduced complex glycan adducts compared to wild-type, is retained in the Golgi rather than trafficking to the plasma membrane (24% of wild-type surface expression by biotinylation), and causes altered Golgi and cellular morphology. Surface biotinylation, immunohistochemistry, electron microscopy, biochemical analysis of glycosylation Neurobiology of disease Medium 25152487
2017 KCNC3 R423H mutation results in altered glycosylation and aberrant retention in anterograde/endosomal vesicles, loss of plasma membrane expression, and aberrant intracellular retention of EGFR in mammalian cells; in Drosophila, co-expression of KCNC3 R423H with dEGFR rescues the eye phenotype, implicating indirect effects on EGFR signaling. Mammalian cell expression with immunofluorescence and electrophysiology, Drosophila genetic co-expression rescue experiments PloS one Medium 28467418
2013 Expression of mutant Kv3.3 R424H (equivalent to human R423H) in cultured cerebellar Purkinje cells via lentiviral vector decreases outward current density, broadens action potentials, elevates basal [Ca2+]i, impairs dendrite development, and causes cell death selectively in Purkinje cells; all rescued by blocking P/Q-type Ca2+ channels. Lentiviral expression in mouse cerebellar cultures, patch-clamp electrophysiology, Ca2+ imaging, pharmacological rescue The Journal of physiology Medium 24218544
2018 C-terminal proline deletion (p.Pro583_Pro585del) in KCNC3 causes normal membrane trafficking but slower channel inactivation and decreased sensitivity to actin depolymerizer latrunculin B, linking the C-terminal proline-rich domain to inactivation kinetics and actin-dependent channel regulation. Mammalian cell expression, electrophysiology, latrunculin B pharmacology, immunofluorescence Cerebellum Medium 29949095
2022 Deletion of Kv3.3 (but not Kv3.1) at the calyx of Held presynaptic terminal reduces presynaptic Kv3 channel immunolabelling, increases presynaptic AP duration, facilitates neurotransmitter release, and enhances short-term depression during high-frequency transmission; modeling showed increased vesicle release probability and accelerated activity-dependent vesicle replenishment in the Kv3.3 KO. Kv3.3 KO mice, electrophysiology, immunolabelling, computational modeling of synaptic transmission eLife High 35510987
2020 In auditory brainstem, LSO neurons absolutely require Kv3.3 subunits for fast AP repolarization (half-width doubled in Kv3.3 KO) and to sustain high-frequency firing, while MNTB neurons can utilize either Kv3.1 or Kv3.3 subunits interchangeably; loss of Kv3.3 in LSO increases Ca2+ influx and AP failure rates. Kv3.3 and Kv3.1 knockout mice, patch-clamp electrophysiology, Ca2+ imaging, TEA pharmacology, western blot The Journal of physiology High 32246836
2021 Antisense oligonucleotides (ASOs) directed against Kcnc3 suppress Kv3.3 mRNA and protein in the cerebellum; in mice bearing the G592R SCA13 mutation, this reverses TBK1 overactivation, restores Hax-1 levels, reduces Cd63 (late endosome marker), and rescues rotarod motor performance, without affecting wild-type mice. Intracerebroventricular ASO infusion in wild-type and G592R knock-in mice, western blot, behavioral rotarod testing FASEB journal Medium 34820911
2020 In zebrafish, an infant-onset SCA13 mutation dramatically increases Purkinje cell excitability, stunts dendritic growth, impairs synaptogenesis, and causes rapid cell death during cerebellar development; reducing excitability increases early Purkinje cell survival. An adult-onset mutation reduces excitability during evoked high-frequency spiking without altering basal tonic firing, and does not cause developmental degeneration. Zebrafish in vivo electrophysiology, live imaging of Purkinje cell development, genetic loss-of-function with defined cellular phenotypes eLife Medium 32644043
1992 KCNC3 (Kv3.3) is encoded by at least two exons separated by ~3 kb of intervening sequence; the N-terminal 212 amino acids are encoded by a single exon and the hydrophobic core (from S1 transmembrane segment onward) by a separate exon. The gene was mapped to human chromosome 19. Genomic cloning, cDNA isolation, Southern blotting, chromosomal mapping Genomics High 1740329
2022 A missense mutation G434V in Kcnc3 (in the voltage sensor transmembrane domain) causes complete loss of voltage-gated conductance in electrophysiological recordings, broadening of action potentials, and decreased neuronal firing, resulting in spatial learning deficits in mice. CRISPR knock-in mouse, in vitro electrophysiology of mutant channel, behavioral fear conditioning and spatial learning assays PNAS Medium 35881790
2024 A Kozak sequence variant (c.-6C>A) upstream of KCNC3 increases protein expression by enhanced translation initiation without affecting transcription rate, as demonstrated by luciferase assays, qPCR, and methylation analysis. Luciferase reporter assay, qPCR, methylation analysis in cell transfection system International journal of molecular sciences Medium 39596509
2024 The Kv3.3 E675K variant causes reduced current amplitude and more pronounced cumulative inactivation in Xenopus oocytes; both wild-type and E675K Kv3.3 inactivation is antagonized by increased extracellular potassium, suggesting a mechanism for potential therapeutic intervention. Voltage-clamp recordings in Xenopus oocytes, pharmacological manipulation of extracellular K+ Frontiers in cellular neuroscience Medium 39416683

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nature genetics 229 16501573
2007 Distribution of Kv3.3 potassium channel subunits in distinct neuronal populations of mouse brain. The Journal of comparative neurology 82 17444489
2010 KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial ataxia patients. Human mutation 72 19953606
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
2008 Purkinje-cell-restricted restoration of Kv3.3 function restores complex spikes and rescues motor coordination in Kcnc3 mutants. The Journal of neuroscience : the official journal of the Society for Neuroscience 67 18448641
2016 Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating. Cell 60 26997484
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
1992 Genomic organization, nucleotide sequence, and cellular distribution of a Shaw-related potassium channel gene, Kv3.3, and mapping of Kv3.3 and Kv3.4 to human chromosomes 19 and 1. Genomics 47 1740329
2013 Kv3.3 channels harbouring a mutation of spinocerebellar ataxia type 13 alter excitability and induce cell death in cultured cerebellar Purkinje cells. The Journal of physiology 45 24218544
2008 Kv3.3 channels at the Purkinje cell soma are necessary for generation of the classical complex spike waveform. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 18256249
2003 Inactivation of Kv3.3 potassium channels in heterologous expression systems. The Journal of biological chemistry 44 12923191
2015 Kv3.3 potassium channels and spinocerebellar ataxia. The Journal of physiology 43 26442672
2011 Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13 (SCA13). PloS one 43 21479265
2012 Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13. The Journal of physiology 36 22289912
2008 Protein kinase C modulates inactivation of Kv3.3 channels. The Journal of biological chemistry 35 18539595
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
2013 Mutation in the kv3.3 voltage-gated potassium channel causing spinocerebellar ataxia 13 disrupts sound-localization mechanisms. PloS one 31 24116147
2001 A prominent soma-dendritic distribution of Kv3.3 K+ channels in electrosensory and cerebellar neurons. The Journal of comparative neurology 30 11745647
2000 Kv3.3 potassium channels in lens epithelium and corneal endothelium. Experimental eye research 30 10712820
2021 Ankyrin-R Links Kv3.3 to the Spectrin Cytoskeleton and Is Required for Purkinje Neuron Survival. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 34785580
2015 Functional analysis helps to define KCNC3 mutational spectrum in Dutch ataxia cases. PloS one 25 25756792
2010 Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes. Journal of neurophysiology 25 20357073
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 24 32246836
2005 A C-terminal domain directs Kv3.3 channels to dendrites. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 16354911
2002 Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1-3, 6 and 7 CAG expansions. Journal of neurology 24 12140678
2022 Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse. eLife 23 35510987
2021 Cerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1. Nature communications 22 33741962
2017 A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking. PloS one 21 28467418
2014 KCNC3(R420H), a K(+) channel mutation causative in spinocerebellar ataxia 13 displays aberrant intracellular trafficking. Neurobiology of disease 20 25152487
2008 Sca13. Cerebellum (London, England) 20 18592334
2010 Functional effects of spinocerebellar ataxia type 13 mutations are conserved in zebrafish Kv3.3 channels. BMC neuroscience 19 20712895
2006 Immunohistochemical localisation of the voltage gated potassium ion channel subunit Kv3.3 in the rat medulla oblongata and thoracic spinal cord. Brain research 18 16403474
2020 Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo. eLife 14 32644043
2010 Precise localization of the voltage-gated potassium channel subunits Kv3.1b and Kv3.3 revealed in the molecular layer of the rat cerebellar cortex by a pre-embedding immunogold method. Histochemistry and cell biology 14 20857303
2008 Subcellular localization of the voltage-gated potassium channels Kv3.1b and Kv3.3 in the cerebellar dentate nucleus of glutamic acid decarboxylase 67-green fluorescent protein transgenic mice. Neuroscience 14 18682278
2011 Kv3.1b and Kv3.3 channel subunit expression in murine spinal dorsal horn GABAergic interneurones. Journal of chemical neuroanatomy 12 21440618
2005 Spinocerebellar ataxia with mental retardation (SCA13). Cerebellum (London, England) 12 15895558
2017 SCA13 causes dominantly inherited non-progressive myoclonus ataxia. Parkinsonism & related disorders 10 28216058
2010 Kv3.3 immunoreactivity in the vestibular nuclear complex of the rat with focus on the medial vestibular nucleus: targeting of Kv3.3 neurones by terminals positive for vesicular glutamate transporter 1. Brain research 10 20471378
2021 Knockdown of lnc-KCNC3-3:1 Alleviates the Development of Atherosclerosis via Downregulation of JAK1/STAT3 Signaling Pathway. Frontiers in cardiovascular medicine 8 34540913
2021 Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 8 34820911
2018 C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity. Cerebellum (London, England) 8 29949095
2013 Mesial temporal lobe epilepsy in a patient with spinocerebellar ataxia type 13 (SCA13). The International journal of neuroscience 7 23215817
2021 Toe Walking as the Initial Symptom of a Spinocerebellar Ataxia 13 in a Patient Presenting with a Mutation in the KCNC3 Gene. Global medical genetics 4 35169784
2016 Voltage-Gated K+ Channel, Kv3.3 Is Involved in Hemin-Induced K562 Differentiation. PloS one 4 26849432
2023 Epilepsy as the symptom of a spinocerebellar ataxia 13 in a patient presenting with a mutation in the KCNC3 gene. BMC neurology 2 37365508
2022 A novel giant non-cholinergic striatal interneuron restricted to the ventrolateral striatum coexpresses Kv3.3 potassium channel, parvalbumin, and the vesicular GABA transporter. Molecular psychiatry 2 33190145
2022 A missense mutation in Kcnc3 causes hippocampal learning deficits in mice. Proceedings of the National Academy of Sciences of the United States of America 2 35881790
2024 Kv3.3 Expression Enhanced by a Novel Variant in the Kozak Sequence of KCNC3. International journal of molecular sciences 1 39596509
2024 A novel KCNC3 gene variant in the voltage-dependent Kv3.3 channel in an atypical form of SCA13 with dominant central vertigo. Frontiers in cellular neuroscience 0 39416683