Affinage

KCNA1

Potassium voltage-gated channel subfamily A member 1 · UniProt Q09470

Length
495 aa
Mass
56.5 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNA1 encodes Kv1.1, a voltage-gated delayed-rectifier K+ channel that assembles cotranslationally into Shaker-family homo- and heterotetramers (with Kv1.2, Kv1.4, Kv1.5) and conducts a dendrotoxin-sensitive low-threshold K+ current that dampens neuronal excitability (PMID:7517498, PMID:8126562, PMID:12611922). The protein localizes to axonal juxtaparanodes, presynaptic terminals, somata, and proximal dendrites, where it sets the membrane potential, controls presynaptic neurotransmitter release, and enforces temporal precision of action potential firing (PMID:8046438, PMID:14534254, PMID:23466697). Through these roles Kv1.1 sets mechanosensory thresholds in DRG mechanoreceptors via Kv1.1/Kv1.2 heteromers (PMID:23473320), constrains motor-nerve axon excitability under metabolic stress (PMID:22609489), and acts as a homeostatic brake on intrinsic excitability in hippocampal pyramidal neurons (PMID:31774395). Channel gating and surface availability are tuned by multiple inputs: palmitoylation at C243 and sialylation shift voltage dependence (PMID:15837928, PMID:8702582); arachidonic acid released by iPLA2 accelerates gating (PMID:7852365); PKA phosphorylation governs cytoplasm-to-membrane trafficking (PMID:12681381, PMID:23774215); PKC inhibits current through a Rho GTPase pathway (PMID:10409113); Gβγ and the aldoketoreductase β-subunit Kvβ1 modulate N-type inactivation (PMID:10064591, PMID:18222921); and an mTOR–miR-129–HuD axis controls dendritic Kv1.1 mRNA translation (PMID:17023663, PMID:23836929). In the kidney distal convoluted tubule Kv1.1 colocalizes with TRPM6 and sets a favorable membrane potential for Mg2+ reabsorption (PMID:19307729). Dominant-negative and loss-of-function KCNA1 mutations cause episodic ataxia type 1, hypomagnesemia, paroxysmal kinesigenic dyskinesia, and epileptic encephalopathy, acting either by ER retention/aggregation of heterotetramers or by altered channel kinetics (PMID:9526001, PMID:11773313, PMID:19307729, PMID:29294000, PMID:31586945); neuron-restricted Kv1.1 loss alone is sufficient to drive epilepsy and brain-driven cardiorespiratory dysregulation underlying SUDEP (PMID:20392939, PMID:31978607).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1994 High

    Established that Kv1.1 is itself a pore-forming subunit producing a functional delayed-rectifier K+ current and that it assembles selectively with Shaker-family subunits, defining the molecular building block.

    Evidence Stable mammalian expression with whole-cell patch clamp and pharmacology; in vitro translation, immunopurification, and pulse-chase of cotranslational assembly

    PMID:7517498 PMID:8126562

    Open questions at the time
    • Subunit stoichiometry in native tissue not resolved
    • Glycosylation role left open for surface trafficking
  2. 1994 High

    Defined the subcellular distribution of Kv1.1 to juxtaparanodes, synaptic terminals, somata, and dendrites, anchoring later excitability functions to specific neuronal compartments.

    Evidence Immunocytochemistry of mouse brain sections, contrasted with Kv1.2

    PMID:8046438

    Open questions at the time
    • Did not establish functional consequence of compartmental targeting
    • Targeting/anchoring mechanism unknown
  3. 1996 High

    Identified lipid- and glycan-based modulation of voltage sensing, showing arachidonic acid and sialic acid residues tune Kv1.1 gating without altering surface expression.

    Evidence Patch clamp in Sf9 with iPLA2 and fatty acid application; expression in glycosylation-deficient CHO Lec cells with sialidase treatment

    PMID:7852365 PMID:8702582

    Open questions at the time
    • Physiological source of arachidonic acid in vivo not defined
    • Whether sialylation state is regulated in neurons unknown
  4. 1998 Medium

    Demonstrated through knockdown and knockout that Kv1.1 is required for hippocampal memory and for nociceptive/antinociceptive signaling, moving from biophysics to organismal function.

    Evidence Antisense knockdown with patch clamp and behavior; Kcna1 knockout mice with nociception assays

    PMID:9114006 PMID:9718989

    Open questions at the time
    • Single-lab behavioral findings
    • Circuit-level basis of memory deficit not dissected
  5. 1999 High

    Resolved the dominant-negative disease mechanism, showing truncated/EA1 subunits coassemble with wild-type and either trap heterotetramers in the ER or alter gating in defined stoichiometries.

    Evidence GH3/oocyte co-expression, double IP, subcellular fractionation, confocal imaging, TEA-tagging, tandem-linked subunits, single-channel analysis

    PMID:10428758 PMID:9334228 PMID:9526001

    Open questions at the time
    • ER quality-control machinery retaining mutant channels not identified
    • Genotype–phenotype severity correlation incomplete
  6. 1999 High

    Identified protein partners and signaling inputs (Gβγ, PKC/Rho, Kvβ1, KCNE4) that regulate Kv1.1 current and inactivation, expanding the channel into a regulated signaling node.

    Evidence GST pulldown and Co-IP for Gβγ; phorbol ester/C3 toxin and mutagenesis for PKC; oocyte/HEK co-expression and confocal colocalization for KCNE4; enzymatic reconstitution for Kvβ1

    PMID:10064591 PMID:10409113 PMID:12944270 PMID:18222921

    Open questions at the time
    • Physiological contexts engaging each modulator not established
    • Direct structural interfaces largely undefined
  7. 2003 High

    Quantified Kv1.1's contribution to the low-threshold K+ current in auditory neurons and established its in vivo role in temporal precision, with partial subunit compensation by Kv1.2/Kv1.6.

    Evidence Patch clamp in Kcna1-null brainstem slices, DTX-K pharmacology, and in vivo single-unit recordings in VCN/MNTB

    PMID:11290530 PMID:12611922 PMID:14534254 PMID:16672305

    Open questions at the time
    • Mechanism of heteromeric compensation not fully resolved
    • Contribution of accessory subunits in vivo unquantified
  8. 2005 High

    Mapped post-translational palmitoylation at C243 as a voltage-sensing modulator, linking membrane attachment of the S2-S3 linker to gating.

    Evidence [3H]palmitate labeling, mutagenesis, and patch clamp in Sf9 cells

    PMID:15837928

    Open questions at the time
    • Palmitoyl-transferase responsible not identified
    • Dynamic regulation of palmitoylation in neurons unknown
  9. 2006 High

    Established translational control of dendritic Kv1.1 by mTOR, later refined into a bidirectional mTOR–miR-129–HuD axis, explaining activity-dependent and disease-associated changes in channel abundance.

    Evidence Rapamycin/NMDA blockade with Kaede local-synthesis reporter; miR-129 reporters, HuD RIP, and competitive binding assays

    PMID:17023663 PMID:23836929

    Open questions at the time
    • Upstream signals setting mTOR tone in dendrites not defined
    • Selectivity of miR-129/HuD for Kv1.1 vs other targets unclear
  10. 2009 High

    Extended Kv1.1 function beyond neurons to the kidney DCT, where it colocalizes with TRPM6 and a dominant-negative mutation causes hypomagnesemia by abolishing the favorable membrane potential for Mg2+ reabsorption.

    Evidence Positional cloning, HEK patch clamp with wild-type co-expression, kidney immunohistochemistry; systematic N255 mutagenesis with surface biotinylation

    PMID:19307729 PMID:19903818

    Open questions at the time
    • Whether DCT Kv1.1 is regulated by hormonal Mg2+ signals unknown
    • Channel partners in renal epithelium beyond TRPM6 not defined
  11. 2013 High

    Defined Kv1.1's presynaptic and mechanosensory roles, showing it brakes neurotransmitter release and sets DRG mechanical thresholds, and connected it to the LGI1–ADAM23 presynaptic complex.

    Evidence MEA recordings and DTX-κ in Kcna1-null hippocampus; toxin profiling and dominant-negative transgenics in DRG with behavior; patient-IgG transfer with patch clamp and LTP

    PMID:23466697 PMID:23473320 PMID:30346486

    Open questions at the time
    • Molecular basis of Kv1.1 mechanosensitivity not structurally defined
    • How LGI1–ADAM23 stabilizes presynaptic Kv1.1 mechanistically unresolved
  12. 2020 High

    Demonstrated that neuron-restricted loss of Kv1.1 is sufficient to produce epilepsy and brain-driven cardiorespiratory dysregulation, localizing SUDEP-relevant phenotypes to the central nervous system.

    Evidence Synapsin1-Cre conditional Kcna1 knockout with EEG, ECG, plethysmography; earlier autonomic pharmacological dissection in global knockouts

    PMID:20392939 PMID:31978607

    Open questions at the time
    • Specific neuronal circuits driving lethal events not pinpointed
    • Therapeutic reversibility not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse regulatory inputs (palmitoylation, PKA/PKC, Gβγ, mTOR-miR-129-HuD, RNA editing) are integrated in vivo to set Kv1.1 availability in specific compartments remains unresolved.
  • No unified model of compartment-specific regulation
  • Interplay between transcriptional, translational, and post-translational control untested in native neurons

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-112316 Neuronal System 4 R-HSA-382551 Transport of small molecules 2
Partners
ADAM23KCNA2KCNA4KCNAB1KCNE4LGI1TRPM6
Complex memberships
Kv1 (Shaker) channel tetramerKv1.1/Kv1.2 heteromeric channelKv1.1/Kvβ1 channel complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Kv1.1 forms functional homomultimeric channels when expressed in mammalian cell lines, producing a delayed-rectifier type K+ current sensitive to dendrotoxin, charybdotoxin, and other pharmacological agents. Biophysical characterization showed it resembles the K+ channel in C6 glioma cells and astrocytes. Stable expression in mammalian cell lines, whole-cell patch clamp, pharmacological profiling Molecular pharmacology High 7517498
1994 Kv1.1 protein is localized to synaptic terminals, somata, juxta-paranodal regions of myelinated axons, unmyelinated axons, specialized junctions among axons, and proximal dendrites in the mouse brain, with region-specific distribution distinct from Kv1.2. Immunocytochemistry in mouse brain sections The Journal of neuroscience High 8046438
1994 Kv1.1 assembles cotranslationally with other Shaker-like subunits (Kv1.4) but not with non-Shaker Kv2.1; N207 glycosylation occurs but is not required for subunit assembly, surface transport, or function; surface channels exist as two species (~57 and ~59 kDa) with precursor-product relationship. Immune purification of in vitro translations and transfected mouse L-cells, pulse-chase metabolic labeling, site-directed mutagenesis of glycosylation site, SDS-PAGE The Journal of neuroscience High 8126562
1995 Ca2+-independent phospholipase A2 (iPLA2) modulates Kv1.1 channel kinetics by releasing arachidonic acid, which accelerates both activation and induces inactivation of the channel. The effect is arachidonic-acid specific and independent of eicosanoid metabolites. Whole-cell patch clamp of Sf9 cells expressing human Kv1.1, intracellular administration of iPLA2, mechanism-based inhibitor, exogenous fatty acid application The Journal of biological chemistry High 7852365
1996 Sialic acid residues on Kv1.1 modulate its voltage dependence of activation (shifting V1/2 to more positive voltages when sialidation is prevented) and slow activation kinetics; sialic acids act as negative surface charges that influence the local electric field at the voltage sensor. Glycosylation is not required for cell surface expression. Expression of Kv1.1 in glycosylation-deficient CHO Lec mutant cell lines, whole-cell patch clamp, sialidase treatment, Ca2+ application The Journal of biological chemistry High 8702582
1997 Antisense oligonucleotide-mediated knockdown of Kv1.1 in hippocampal neurons reduces late-rectifying K+ current in dentate granule cells and impairs associative memory (passive avoidance and spatial memory tasks) in mice and rats, demonstrating Kv1.1 is required for hippocampus-dependent memory formation. Intracerebroventricular antisense oligonucleotide injection, whole-cell patch clamp of dentate granule cells, behavioral testing (passive avoidance, Morris water maze) Proceedings of the National Academy of Sciences Medium 9114006
1997 Truncated Kv1.1 (Kv1.1N206Tag) forms heteromultimeric complexes with native Kv1.4 and Kv1.5 channels and traps these complexes in the endoplasmic reticulum, preventing surface expression — establishing a dominant-negative mechanism via ER retention. Transient expression in GH3 cells, double immunoprecipitation, subcellular fractionation, immunofluorescence/confocal microscopy The Journal of biological chemistry High 9334228
1998 Episodic ataxia type 1 (EA1) mutations in Kv1.1 affect channel function by two mechanisms: dominant negative effects (most mutations), or haploinsufficiency (R239S and F249I, which show reduced protein levels). EA subunits coassemble with wild-type subunits in mixed stoichiometries. Channels bearing EA mutations show lower current amplitudes and altered gating. Expression of EA mutant cRNAs in Xenopus oocytes, co-injection experiments, TEA-tagging to discriminate subunit contribution, Western blot The Journal of neuroscience High 9526001
1998 Kv1.1 loss-of-function (Kcna1 knockout) causes thermal hyperalgesia and increased formalin-induced nociception, and blunts morphine-induced antinociception, establishing Kv1.1 as a regulator of nociceptive and antinociceptive signaling. Kcna1 knockout mice, paw flick assay, hot plate assay, formalin test, morphine antinociception assay Neuroscience letters Medium 9718989
1999 EA1 mutations V408A and E325D in Kv1.1, when co-assembled with Kv1.2 using tandem-linked subunits, produce heteromeric channels with altered kinetics of activation, deactivation, C-type inactivation, and voltage dependence. V408A reduces mean open duration ~3-fold in single-channel analysis, destabilizing the open state of both homomeric and heteromeric channels. Tandemly linked subunit expression in Xenopus oocytes, single-channel patch clamp, macroscopic current analysis FASEB journal High 10428758
1999 Protein kinase C (PKC) activation inhibits Kv1.1 current by up to 90% via a mechanism requiring a C3 exoenzyme substrate (Rho GTPase pathway), without altering activation gating or reducing membrane channel protein. Direct phosphorylation of Kv1.1 by PKC was not responsible. Xenopus oocyte expression, phorbol ester treatment, PKC inhibitors, site-directed mutagenesis of PKC phosphorylation sites, Western blot, botulinum toxin C3 injection The American journal of physiology Medium 10409113
1999 Dendrotoxin K (DTXk) selectively inhibits Kv1.1-containing channels; its K3 residue in the 310-helical N-terminal region is critical for Kv1.1 recognition (K3A mutation causes ~1246-fold loss of potency), while W25 and K26 in the beta-turn are also important for toxin-channel interaction. Site-directed mutagenesis of DTXk, radioligand binding competition assay with [125I]DTXk and [125I]alphaDTX to rat brain membranes, two-electrode voltage clamp in Xenopus oocytes expressing Kv1.1 European journal of biochemistry High 10429207
1999 G protein beta-gamma (Gbeta1gamma2) subunits directly interact with Kv1.1 and Kvbeta1.1, promote co-assembly of more Kvbeta1.1 with Kv1.1, and increase the extent of N-type (A-type) inactivation of Kv1.1/Kvbeta1.1 channels. This effect is occluded by microfilament disruption and requires co-expression during channel assembly rather than acute application. Xenopus oocyte co-expression, GST pulldown of Gbeta1gamma2 with Kv1.1/Kvbeta1.1 fusion fragments, co-immunoprecipitation, electrophysiology, C-terminal betaARK fragment scavenging The EMBO journal High 10064591
1999 The R417stop truncation mutation in Kv1.1 (EA1) impairs both tetramerization with wild-type subunits and membrane targeting of heterotetramers, trapping channels intracellularly. Other EA1 mutations (V404I, P244H) do not affect tetramerization or trafficking but alter channel kinetics. Xenopus oocyte expression, electrophysiology, pharmacological subunit discrimination, confocal laser scanning microscopy of EGFP-tagged subunits The Journal of physiology High 11773313
2001 EA1 nonsense mutations in Kv1.1 cause intracellular aggregation and detergent insolubility of the mutant protein, which can be transferred to co-assembled Kv1 alpha- and Kvbeta-subunits. EA1 missense mutations, in contrast, do not alter folding or trafficking compared to wild-type. Heterologous expression, detergent solubility assay, immunostaining, co-assembly analysis The Journal of biological chemistry Medium 11679591
2003 Kv1.1 subunits contribute ~50% of the low voltage-activated potassium current (IKL) in auditory MNTB neurons. Kcna1 knockout mice show approximately halved IKL amplitude, doubled action potential firing, and halved rheobase. Residual IKL in knockout neurons is carried by Kv1.2/Kv1.6-containing channels (DTX-sensitive). Whole-cell patch clamp in brainstem slices from Kcna1-null mice and wild-type littermates, dendrotoxin pharmacology The Journal of physiology High 12611922
2003 Kv1.1 glycosylation (N-linked, at S1-S2 linker) does not affect protein stability, cellular localization, or trafficking to the cell surface, in contrast to Kv1.4. A pore region determinant in Kv1.1 vs Kv1.4 dictates whether glycosylation influences trafficking. Prevention of N-glycosylation (tunicamycin, mutagenesis), Western blot for protein stability, immunocytochemistry for cellular localization, chimeric channel construction The Journal of biological chemistry High 14688283
2003 Kv1.1 is expressed in the medial nucleus of the trapezoid body (MNTB) and is required for temporal precision (low jitter) in auditory signal processing in vivo; Kcna1-null mice show increased first-spike latency jitter in VCN and MNTB neurons and failure to follow high-frequency amplitude-modulated stimuli. In vivo single-unit recordings from VCN and MNTB neurons of Kcna1-null and wild-type mice during auditory stimulation The Journal of neuroscience High 14534254
2003 Truncation of Kv1.1 at amino acid 230 (mceph mutation, 11-bp deletion) in mice causes megencephaly; the truncated protein lacks C-terminal domains, and sequestration of Kv1.2 and Kv1.3 proteins is observed (reduced protein levels despite normal mRNA), suggesting dominant interaction at the protein level. Seizures occur in these mice. Positional cloning, sequencing, immunoblot for Kv1.2/Kv1.3 protein levels, in situ hybridization for mRNA, EEG The European journal of neuroscience Medium 14686897
2005 Human Kv1.1 is palmitoylated at cysteine C243 in the cytosolic S2-S3 linker domain; preventing palmitoylation at C243 by mutagenesis causes a 20-mV leftward shift in the current-voltage relationship, implicating palmitoylation at C243 in modulating voltage sensing through protein-membrane interactions. Heterologous expression in Sf9 cells, [3H]palmitate radiolabeling, chemical stability studies, site-directed mutagenesis, whole-cell patch clamp Proceedings of the National Academy of Sciences High 15837928
2006 Kv1.1-containing channels (identified by dendrotoxin-K) underlie low-threshold K+ current (Ikl) in MNTB neurons and are critical for temporal precision of spike initiation; partial (~50%) reduction of Ikl by 3 nM DTX-K or Kcna1 knockout similarly increases AP jitter and latency, especially at high stimulation rates. Whole-cell patch clamp in mouse brain slices, selective DTX-K pharmacology at multiple concentrations, comparison with Kcna1-/- mice Journal of neurophysiology High 16672305
2006 mTOR activity suppresses Kv1.1 mRNA translation in dendrites; inhibition of mTOR with rapamycin or of NMDA receptors increases Kv1.1 protein in hippocampal neuron dendrites (but not axons). Local dendritic synthesis of Kv1.1 was demonstrated using a Kaede photoconvertible reporter. Rapamycin treatment of hippocampal neurons, Kv1.1-Kaede reporter for local protein synthesis, immunostaining, NMDA receptor blockade Science High 17023663
2006 EA1 mutations E325D, V404I, V408A, and I177N in Kv1.1 alter N-type inactivation properties of heteromeric Kv1.4-1.1 channels co-assembled with Kvbeta1.1 or Kvbeta1.2: they decrease the rate and degree of N-type inactivation, accelerate recovery from fast inactivation, and shift steady-state inactivation voltage dependence. Expression of tandemly linked Kv1.4-1.1 constructs with EA1 mutations in Xenopus oocytes, two-electrode voltage clamp The European journal of neuroscience High 17156368
2008 Kvbeta1 is a functional aldoketoreductase; oxidation of the NADPH cofactor bound to Kvbeta1 (either enzymatically by a substrate or non-enzymatically by H2O2 or NADP+) causes a large increase in open Kv1.1 channel current. This cofactor oxidation rate is ~2-fold faster at 0 mV than at -100 mV, indicating that Kv1.1 voltage-dependent conformational changes regulate Kvbeta1 enzymatic activity. Patch clamp of Kv1.1 + Kvbeta1 expressed in oocytes, substrate addition, H2O2/NADP+ treatment, deletion mutagenesis of Kv1.1 C-terminus The Journal of biological chemistry High 18222921
2009 A missense mutation N255D in KCNA1 (S3 transmembrane segment) causes autosomal dominant hypomagnesemia by creating a non-functional channel with dominant negative effect on wild-type Kv1.1. Kv1.1 is expressed in the kidney distal convoluted tubule (DCT) where it colocalizes with the Mg2+ transporter TRPM6 on the luminal membrane, establishing a favorable membrane potential for TRPM6-mediated Mg2+ reabsorption. Positional cloning, patch clamp of N255D-expressing HEK cells, co-expression with wild-type, immunohistochemistry of kidney sections for Kv1.1/TRPM6 colocalization The Journal of clinical investigation High 19307729
2009 Systematic mutagenesis of Kv1.1 N255 confirms that asparagine at position 255 is required for normal voltage dependence and kinetics of gating; charged substitutions (N255D, N255E, N255Q) abolish function, while small hydrophobic or polar substitutions permit conduction with shifted activation voltage and faster activation kinetics. Expression of N255 mutants in HEK293 cells, cell surface biotinylation, whole-cell patch clamp The Journal of biological chemistry High 19903818
2010 Kcna1-null mice display interictal cardiac abnormalities (AV conduction blocks, bradycardia, premature ventricular contractions) caused by excessive parasympathetic tone rather than intrinsic cardiac defect. Kv1.1 is expressed in juxtaparanodes of the vagus nerve; autonomic blockade (atropine) eliminates the AV conduction blocks, demonstrating brain-driven cardiac dysfunction. Simultaneous video EEG-ECG recordings in Kcna1-null mice, autonomic pharmacological blockade (atropine, propranolol), immunohistochemistry of vagus nerve The Journal of neuroscience High 20392939
2011 NRG1 via its receptor ErbB4 increases the intrinsic excitability of fast-spiking parvalbumin-positive interneurons by decreasing voltage threshold for action potentials through Kv1.1 channels; this was established by pharmacological and genetic manipulation of ErbB4 in parvalbumin interneurons. Whole-cell patch clamp of FS-PV interneurons, ErbB4 conditional knockout in PV interneurons, NRG1 application, Kv1.1 pharmacology Nature neuroscience High 22158511
2013 mTOR activity regulates Kv1.1 mRNA translation via miR-129: when mTOR is active, miR-129 represses Kv1.1 translation; when mTOR is inactive, the RNA-binding protein HuD is freed from high-affinity target mRNA degradation, binds Kv1.1 mRNA, and promotes its translation. This establishes a bidirectional mTOR-HuD-miR-129 axis controlling dendritic Kv1.1 expression. miRNA identification, miR-129 reporter assays, HuD RNA immunoprecipitation, mTOR inhibition (rapamycin), competitive binding assays for HuD The Journal of cell biology High 23836929
2013 Kv1.1-Kv1.2 heteromers mediate a mechanosensitive K+ current (IKmech) in dorsal root ganglion mechanoreceptors; mechanosensitivity is attributed specifically to the Kv1.1 subunit through facilitation of voltage-dependent open probability. IKmech acts as a 'brake' opposing depolarization from MS cation currents in C-HTMRs, setting mechanical threshold. Dominant-negative Kv1.1 expression or Kv1.1 inhibition causes severe mechanical allodynia. Toxin profiling of IKmech, transgenic mouse studies (Kv1.1 dominant negative), whole-cell patch clamp of DRG mechanoreceptors, behavioral mechanical sensitivity testing Neuron High 23473320
2013 Loss of Kv1.1 in Kcna1-null mice enhances synaptic neurotransmitter release at mossy fiber and perforant path terminals in the CA3 region, reducing spike timing precision and producing pathologic high-frequency oscillations (fast ripples). This was recapitulated in wild-type slices with DTX-κ, confirming Kv1.1's role in presynaptic release control. Multielectrode array extracellular recordings in hippocampal slices, Kcna1-null mice, micro-dissection, paired-pulse ratio, DTX-κ pharmacology Neurobiology of disease High 23466697
2013 Oncogenic stress induces KCNA1 upregulation and redistribution from cytoplasm to the plasma membrane in a PKA-dependent manner: PKA phosphorylation at S446 retains Kv1.1 in the cytoplasm, and loss of PKA-induced phosphorylation (or PKA inhibition) allows membrane relocation. Membrane-localized Kv1.1 changes membrane potential and triggers cellular senescence, restricting oncogenesis. Loss-of-function genetic screen, phosphomimetic mutagenesis (S446), PKA activity manipulation, membrane potential measurements, transformation assays Cancer research Medium 23774215
2014 During temporal lobe epileptogenesis, two sequential phases of Kv1.1 repression occur: (1) an initial mTOR-dependent phase where mTOR activity reduces Kv1.1 expression, lowering AP firing threshold in CA1 pyramidal neurons; (2) a later mTOR-independent phase maintained by increased miR-129-5p, which persistently represses Kv1.1 mRNA translation. Kainic acid epilepsy model in rats, rapamycin treatment, miR-129-5p quantification, in vivo whole-cell patch clamp of CA1 neurons Neurobiology of disease Medium 25270294
2018 LGI1 antibodies (patient-derived IgG) disrupt LGI1 interaction with ADAM23 (which interacts with presynaptic Kv1.1) and cause decreased total and synaptic levels of Kv1.1 in hippocampal neurons, leading to neuronal hyperexcitability, increased presynaptic glutamate release probability, and impaired long-term potentiation. Patient IgG cerebroventricular infusion in mice, confocal analysis of hippocampal slices, whole-cell patch clamp of dentate gyrus and CA1 neurons, field potential LTP recordings Brain High 30346486
2018 Two novel KCNA1 mutations (L319R and N255K) causing paroxysmal kinesigenic dyskinesia produce reduced K+ currents with altered gating and dominant negative effects on wild-type Kv1.1 in HEK293 cells; L319R also accelerates protein degradation via the proteasome pathway and disrupts membrane expression. Whole-exome sequencing, patch clamp in HEK293 cells, Western blot, proteasome inhibitor studies, surface expression assay Human molecular genetics Medium 29294000
2019 A recessive homozygous KCNA1 variant (p.Val368Leu) in the pore domain abolishes channel function; heterozygous co-expression with wild-type produces no dominant negative effect, distinguishing this from all previously described autosomal dominant KCNA1 mutations. This establishes KCNA1 loss of function via a recessive mechanism causing neonatal epileptic encephalopathy. Whole-exome sequencing, patch clamp of mutant-expressing cells, co-expression with wild-type Journal of medical genetics Medium 31586945
2020 Neuron-specific conditional Kcna1 knockout (using Synapsin1-Cre) is sufficient to cause epilepsy, premature death, and cardiorespiratory dysregulation, demonstrating that the brain-driven (neuronal) loss of Kv1.1 alone — without cardiac Kv1.1 deficiency — underlies SUDEP-associated phenotypes. Conditional knockout mice (floxed Kcna1 × Synapsin1-Cre), EEG, ECG, plethysmography, molecular confirmation of tissue-specific deletion Neurobiology of disease High 31978607
2003 KCNE4 beta-subunit specifically inhibits Kv1.1 and Kv1.3 but not Kv1.2, Kv1.4, Kv1.5, or Kv4.3 homomeric channels; it also reduces current through Kv1.1/Kv1.2 heteromers. Confocal microscopy and Western blotting show Kv1.1 and KCNE4 co-localize at the cell surface. Xenopus oocyte and HEK293 cell co-expression, whole-cell patch clamp, confocal microscopy, Western blot Biophysical journal High 12944270
1995 Kv1.1 channel activity is required for thymocyte development: dendrotoxin blockade of Kv1.1 (and charybdotoxin blockade of Kv1.3) reduces thymocyte yield and alters developmental progression of CD4-CD8- thymocytes in fetal thymic organ culture. Patch clamp of murine thymocytes, RT-PCR, fetal thymic organ culture with DTX and CTX peptide blockers The Journal of biological chemistry Medium 7673227
1998 Cyclic AMP elevation in C6 glioma cells accelerates Kv1.1 mRNA degradation, leading to reduced Kv1.1 protein and decreased sustained K+ current. Kv1.1 contributes to setting the resting membrane potential (DTX-I blocks 96% of sustained K+ current, shifting Vm from -40 to -7 mV). cAMP elevation (forskolin/IBMX) in C6 glioma, Northern blot, Western blot, whole-cell patch clamp, DTX-I pharmacology Proceedings of the National Academy of Sciences Medium 9636212
2003 Analysis of phosphorylation-dependent modulation shows PKA activation causes phosphorylation of intracellular Kv1.1 protein, followed by rapid translocation to the plasma membrane and increased current amplitude with altered voltage dependence. PKC activation does not directly phosphorylate Kv1.1 but induces Kv1.1 protein synthesis. Stable HEK293 transfection with Kv1.1, PKA/PKC activators, phospho-specific immunoprecipitation, subcellular fractionation, whole-cell patch clamp Neuropharmacology Medium 12681381
2011 RNA editing of Kv1.1 at position I400V generates 4-aminopyridine-insensitive Kv1.1 channels; fourfold increased I400V RNA editing in the entorhinal cortex of chronic epileptic rats accounts for the reduced ictogenic potential of 4-AP in this tissue. Sequencing of Kv1.1 mRNA from epileptic rat brain, two-electrode voltage clamp in Xenopus oocytes expressing edited vs unedited Kv1.1 Epilepsia Medium 21371023
2012 The V408A knock-in mutation in Kv1.1 causes spontaneous myokymic discharges in motor nerve; two-photon Ca2+ imaging shows abnormal spontaneous Ca2+ signals in V408A motor nerve axons. Myokymic activity is exacerbated by fatigue, ischemia, and low temperature, identifying juxtaparanodal Kv1.1 as critical for dampening motor nerve axon excitability under stress. V408A knock-in mice, in vivo nerve-muscle preparations, two-photon Ca2+ imaging of motor nerve, compound muscle action potential recording, nerve axotomy Neurobiology of disease High 22609489
2019 Kv1.1 contributes to homeostatic depression of intrinsic excitability in CA1 pyramidal neurons in vivo: theta-burst-induced depression of excitability was attenuated by DTX-K (Kv1.1 blocker), indicating an axonal Kv1.1 mechanism distinct from dendritic Ih. Whole-cell patch clamp in anesthetized rats in vivo, theta-burst stimulation, dendrotoxin K pharmacology eLife Medium 31774395
1999 Kv1.1 is expressed in Kv1.1-positive cells in the absence of Kv1.1, ~50% of IKL remains and is still dendrotoxin-sensitive, suggesting Kv1.2 and/or Kv1.6 compensate in part by forming DTX-sensitive channels; full IKL requires Kv1.1 subunit participation. Patch clamp in MNTB neurons from Kcna1-null mice, dendrotoxin pharmacology The Journal of physiology Medium 12611922

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Molecular pharmacology 700 7517498
1994 Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 337 8046438
2006 Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites. Science (New York, N.Y.) 228 17023663
2000 Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability. Annals of neurology 191 11026449
2018 LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain : a journal of neurology 186 30346486
2010 Kv1.1 potassium channel deficiency reveals brain-driven cardiac dysfunction as a candidate mechanism for sudden unexplained death in epilepsy. The Journal of neuroscience : the official journal of the Society for Neuroscience 184 20392939
2011 Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and acts in epilepsy. Nature neuroscience 152 22158511
2003 Hyperexcitability and reduced low threshold potassium currents in auditory neurons of mice lacking the channel subunit Kv1.1. The Journal of physiology 119 12611922
2013 Kv1.1 channels act as mechanical brake in the senses of touch and pain. Neuron 111 23473320
2009 A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia. The Journal of clinical investigation 111 19307729
1994 The brain Kv1.1 potassium channel: in vitro and in vivo studies on subunit assembly and posttranslational processing. The Journal of neuroscience : the official journal of the Society for Neuroscience 108 8126562
2013 Degradation of high affinity HuD targets releases Kv1.1 mRNA from miR-129 repression by mTORC1. The Journal of cell biology 99 23836929
2002 Potassium channels Kv1.1, Kv1.2 and Kv1.6 influence excitability of rat visceral sensory neurons. The Journal of physiology 98 12042352
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
2012 Kv1.1 and Kv1.2: similar channels, different seizure models. Epilepsia 93 22612818
2003 Decreased temporal precision of auditory signaling in Kcna1-null mice: an electrophysiological study in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 93 14534254
2010 Nerve excitability studies characterize Kv1.1 fast potassium channel dysfunction in patients with episodic ataxia type 1. Brain : a journal of neurology 79 21106501
2000 KV1.1 K(+) channels identification in human breast carcinoma cells: involvement in cell proliferation. Biochemical and biophysical research communications 79 11097830
1998 Episodic ataxia mutations in Kv1.1 alter potassium channel function by dominant negative effects or haploinsufficiency. The Journal of neuroscience : the official journal of the Society for Neuroscience 79 9526001
1999 Developmental seizure susceptibility of kv1.1 potassium channel knockout mice. Developmental neuroscience 78 10575255
2000 Abnormal axonal physiology is associated with altered expression and distribution of Kv1.1 and Kv1.2 K+ channels after chronic spinal cord injury. The European journal of neuroscience 77 10712629
2020 Kv1.1 Channelopathies: Pathophysiological Mechanisms and Therapeutic Approaches. International journal of molecular sciences 74 32331416
2016 Orexin Receptor Antagonism Improves Sleep and Reduces Seizures in Kcna1-null Mice. Sleep 74 26446112
2004 Activity-dependent regulation of the potassium channel subunits Kv1.1 and Kv3.1. The Journal of comparative neurology 74 14755528
1996 Expression of Kv1.1 delayed rectifier potassium channels in Lec mutant Chinese hamster ovary cell lines reveals a role for sialidation in channel function. The Journal of biological chemistry 73 8702582
1997 Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat. Proceedings of the National Academy of Sciences of the United States of America 72 9114006
2020 Clinical Spectrum of KCNA1 Mutations: New Insights into Episodic Ataxia and Epilepsy Comorbidity. International journal of molecular sciences 70 32316562
2006 Kv1.1-containing channels are critical for temporal precision during spike initiation. Journal of neurophysiology 67 16672305
1999 Identification of residues in dendrotoxin K responsible for its discrimination between neuronal K+ channels containing Kv1.1 and 1.2 alpha subunits. European journal of biochemistry 67 10429207
2003 KCNE4 is an inhibitory subunit to Kv1.1 and Kv1.3 potassium channels. Biophysical journal 66 12944270
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
2013 Loss of the Kv1.1 potassium channel promotes pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices. Neurobiology of disease 61 23466697
2007 Manipulation of the potassium channel Kv1.1 and its effect on neuronal excitability in rat sensory neurons. Journal of neurophysiology 58 17855588
2005 The human Kv1.1 channel is palmitoylated, modulating voltage sensing: Identification of a palmitoylation consensus sequence. Proceedings of the National Academy of Sciences of the United States of America 58 15837928
2007 Structural consequences of Kcna1 gene deletion and transfer in the mouse hippocampus. Epilepsia 57 17651419
1999 Distribution in rat brain of binding sites of kaliotoxin, a blocker of Kv1.1 and Kv1.3 alpha-subunits. The Journal of pharmacology and experimental therapeutics 56 10565809
2001 Functional and molecular expression of a voltage-dependent K(+) channel (Kv1.1) in interstitial cells of Cajal. The Journal of physiology 55 11389194
2001 Episodic ataxia type-1 mutations in the Kv1.1 potassium channel display distinct folding and intracellular trafficking properties. The Journal of biological chemistry 54 11679591
2008 Functional coupling between the Kv1.1 channel and aldoketoreductase Kvbeta1. The Journal of biological chemistry 52 18222921
2002 Variable K(+) channel subunit dysfunction in inherited mutations of KCNA1. The Journal of physiology 52 11773313
2010 Kv1.1 and Kv1.3 channels contribute to the degeneration of retinal ganglion cells after optic nerve transection in vivo. Cell death and differentiation 51 19696788
2008 Different residues in channel turret determining the selectivity of ADWX-1 inhibitor peptide between Kv1.1 and Kv1.3 channels. Journal of proteome research 50 18937510
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
2016 Distinctive role of KV1.1 subunit in the biology and functions of low threshold K(+) channels with implications for neurological disease. Pharmacology & therapeutics 49 26825872
2005 Mu opioid receptor activation inhibits GABAergic inputs to basolateral amygdala neurons through Kv1.1/1.2 channels. Journal of neurophysiology 49 16306173
2003 Truncation of the Shaker-like voltage-gated potassium channel, Kv1.1, causes megencephaly. The European journal of neuroscience 49 14686897
1998 Hyperalgesia in mice lacking the Kv1.1 potassium channel gene. Neuroscience letters 49 9718989
1995 Concomitant acceleration of the activation and inactivation kinetics of the human delayed rectifier K+ channel (Kv1.1) by Ca(2+)-independent phospholipase A2. The Journal of biological chemistry 49 7852365
2018 Respiratory dysfunction progresses with age in Kcna1-null mice, a model of sudden unexpected death in epilepsy. Epilepsia 48 29327348
1999 Protein kinase C inhibits Kv1.1 potassium channel function. The American journal of physiology 48 10409113
2008 In the ventral cochlear nucleus Kv1.1 and subunits of HCN1 are colocalized at surfaces of neurons that have low-voltage-activated and hyperpolarization-activated conductances. Neuroscience 47 18424000
2007 A cysteine-rich receptor-like kinase NCRK and a pathogen-induced protein kinase RBK1 are Rop GTPase interactors. The Plant journal : for cell and molecular biology 47 18088316
1999 Fast inactivation of a brain K+ channel composed of Kv1.1 and Kvbeta1.1 subunits modulated by G protein beta gamma subunits. The EMBO journal 47 10064591
1998 Expression of Kv1.1, a Shaker-like potassium channel, is temporally regulated in embryonic neurons and glia. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 9671659
2020 Neuron-specific Kv1.1 deficiency is sufficient to cause epilepsy, premature death, and cardiorespiratory dysregulation. Neurobiology of disease 45 31978607
2018 Functional role of Kv1.1 and Kv1.3 channels in the neoplastic progression steps of three cancer cell lines, elucidated by scorpion peptides. International journal of biological macromolecules 45 29415410
2017 Scn2a deletion improves survival and brain-heart dynamics in the Kcna1-null mouse model of sudden unexpected death in epilepsy (SUDEP). Human molecular genetics 43 28334922
2013 Potassium channel KCNA1 modulates oncogene-induced senescence and transformation. Cancer research 43 23774215
2015 Variability of Potassium Channel Blockers in Mesobuthus eupeus Scorpion Venom with Focus on Kv1.1: AN INTEGRATED TRANSCRIPTOMIC AND PROTEOMIC STUDY. The Journal of biological chemistry 41 25792741
2009 A novel KCNA1 mutation associated with global delay and persistent cerebellar dysfunction. Movement disorders : official journal of the Movement Disorder Society 41 19205071
2018 Familial paroxysmal kinesigenic dyskinesia is associated with mutations in the KCNA1 gene. Human molecular genetics 40 29294000
2014 Rapamycin reveals an mTOR-independent repression of Kv1.1 expression during epileptogenesis. Neurobiology of disease 40 25270294
2015 Novel phenotype associated with a mutation in the KCNA1(Kv1.1) gene. Frontiers in physiology 39 25642194
2003 Kv1.1 and Kv1.3 channels contribute to the delayed-rectifying K+ conductance in rat choroid plexus epithelial cells. American journal of physiology. Cell physiology 38 14602579
2003 Kv1.1 channels of dorsal root ganglion neurons are inhibited by n-butyl-p-aminobenzoate, a promising anesthetic for the treatment of chronic pain. The Journal of pharmacology and experimental therapeutics 37 12538804
1995 Identification of Kv1.1 expression by murine CD4-CD8- thymocytes. A role for voltage-dependent K+ channels in murine thymocyte development. The Journal of biological chemistry 37 7673227
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
2011 RNA editing of Kv1.1 channels may account for reduced ictogenic potential of 4-aminopyridine in chronic epileptic rats. Epilepsia 36 21371023
2008 A novel KCNA1 mutation identified in an Italian family affected by episodic ataxia type 1. Neuroscience 36 18926884
2005 Kv1.1 deletion augments the afferent hypoxic chemosensory pathway and respiration. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 15800194
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
2019 Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia. Journal of medical genetics 35 31586945
2015 Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation. Basic research in cardiology 34 26162324
2007 Kv1.1/1.2 channels are downstream effectors of nitric oxide on synaptic GABA release to preautonomic neurons in the paraventricular nucleus. Neuroscience 34 17869444
2003 Hyperexcitability of CA3 pyramidal cells in mice lacking the potassium channel subunit Kv1.1. Epilepsia 34 14636320
2018 mTOR-dependent alterations of Kv1.1 subunit expression in the neuronal subset-specific Pten knockout mouse model of cortical dysplasia with epilepsy. Scientific reports 32 29476105
2009 Functional analysis of the Kv1.1 N255D mutation associated with autosomal dominant hypomagnesemia. The Journal of biological chemistry 32 19903818
2004 A novel mutation in KCNA1 causes episodic ataxia without myokymia. Human mutation 32 15532032
2020 Progressive cardiorespiratory dysfunction in Kv1.1 knockout mice may provide temporal biomarkers of pending sudden unexpected death in epilepsy (SUDEP): The contribution of orexin. Epilepsia 31 32030748
2006 Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia. Neurogenetics 31 17136396
2018 De novo KCNA1 variants in the PVP motif cause infantile epileptic encephalopathy and cognitive impairment similar to recurrent KCNA2 variants. American journal of medical genetics. Part A 30 30055040
1998 Cyclic AMP regulates potassium channel expression in C6 glioma by destabilizing Kv1.1 mRNA. Proceedings of the National Academy of Sciences of the United States of America 30 9636212
2012 Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature. Neurobiology of disease 29 22609489
2007 Disruption of Kv1.1 N-type inactivation by novel small molecule inhibitors (disinactivators). Bioorganic & medicinal chemistry 29 18226531
1992 Identification of RBK1 potassium channels in C6 astrocytoma cells. Glia 29 1533613
2011 Low-voltage activated Kv1.1 subunits are crucial for the processing of sound source location in the lateral superior olive in mice. The Journal of physiology 28 21224222
2011 Kcna1-mutant rats dominantly display myokymia, neuromyotonia and spontaneous epileptic seizures. Brain research 28 22206926
2008 Novel mutation in KCNA1 causes episodic ataxia with paroxysmal dyspnea. Muscle & nerve 28 17912752
2002 Episodic ataxia type 1 mutations in the human Kv1.1 potassium channel alter hKvbeta 1-induced N-type inactivation. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 12077175
1999 Expression in mammalian cells and electrophysiological characterization of two mutant Kv1.1 channels causing episodic ataxia type 1 (EA-1). The European journal of neuroscience 28 10383630
2003 Analysis of phosphorylation-dependent modulation of Kv1.1 potassium channels. Neuropharmacology 27 12681381
2019 Silencing of KCNA1 suppresses the cervical cancer development via mitochondria damage. Channels (Austin, Tex.) 26 31354026
2019 Kv1.1 contributes to a rapid homeostatic plasticity of intrinsic excitability in CA1 pyramidal neurons in vivo. eLife 26 31774395
2015 Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations. Neurogenetics 26 26395884
2006 Block of neural Kv1.1 potassium channels for neuroinflammatory disease therapy. Annals of neurology 26 17044011
2003 Developmental change in expression and subcellular localization of two shaker-related potassium channel proteins (Kv1.1 and Kv1.2) in the chick tangential vestibular nucleus. The Journal of comparative neurology 26 12746863
1995 Inactivation of the cloned potassium channel mouse Kv1.1 by the human Kv3.4 'ball' peptide and its chemical modification. The Journal of physiology 26 7602512
2012 Kcna1 gene deletion lowers the behavioral sensitivity of mice to small changes in sound location and increases asynchronous brainstem auditory evoked potentials but does not affect hearing thresholds. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 22396426
2008 Kv1.1 expression in microglia regulates production and release of proinflammatory cytokines, endothelins and nitric oxide. Neuroscience 25 19118603
2006 Involvement of Kv1.1 and Nav1.5 in proliferation of gastric epithelial cells. Journal of cellular physiology 25 16331678

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