Affinage

KCND3

A-type voltage-gated potassium channel KCND3 · UniProt Q9UK17

Length
655 aa
Mass
73.5 kDa
Annotated
2026-06-10
100 papers in source corpus 49 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCND3 encodes Kv4.3, the pore-forming subunit of a rapidly inactivating, voltage-gated A-type K+ channel that constitutes the principal molecular correlate of the cardiac transient outward current (Ito) and contributes to neuronal A-type currents (IA) (PMID:8831489, PMID:20371829). In the heart, Kv4.3-mediated Ito sets the action potential plateau and duration: overexpression abbreviates APD while dominant-negative suppression prolongs APD and the QT interval, and increased Ito antagonizes calcineurin/NFAT-driven hypertrophy (PMID:10772652, PMID:15557376). Kv4.3 functions within a macromolecular complex whose biophysics are tuned by auxiliary subunits — KChIP isoforms increase current density, slow inactivation in a Ca2+-dependent manner, and accelerate recovery from inactivation, with KChIP-mediated palmitoylation and N-terminal interactions controlling membrane trafficking and acting as a slow inactivation gate, while dipeptidyl-peptidase-related subunits DPP6/DPPX and DPP10 and the KCNE2 and Kvβ subunits further shape inactivation gating and reconstitute native human Ito kinetics (PMID:12135940, PMID:12006572, PMID:19109250, PMID:15890703, PMID:16738002, PMID:11087728, PMID:20042375). Channel gating is regulated by direct phosphorylation: CaMKII phosphorylates S550 to slow inactivation, and PKCα downregulates current while a long-isoform-specific T504 site governs PKC modulation of closed-state inactivation (PMID:15456698, PMID:21803046, PMID:19675305). Kv4.3 also physically associates with the angiotensin II type-1 receptor, which drives Ang II-induced channel internalization, and sequesters inactive CaMKII at the membrane to suppress its autophosphorylation and downstream L-type Ca2+ current facilitation (PMID:15342638, PMID:21148163). Kv4.3 abundance is controlled at multiple levels — Ang II destabilizes its mRNA through an AT1R/NADPH-oxidase/p38/AUF1 pathway acting on a 3'UTR AU-rich element, phenylephrine suppresses its promoter, NRSF epigenetically silences the gene via histone H4 deacetylation after nerve injury, and thyroid hormone receptors TRα1 and TRβ1 oppositely regulate its transcription (PMID:11249870, PMID:16556864, PMID:18789946, PMID:20006971, PMID:19171649). Loss-of-function KCND3 mutations cause SCA19/22 through ER retention, protein instability, and dominant-negative suppression of wild-type channels, whereas gain-of-function mutations underlie Brugada syndrome, early repolarization syndrome, and atrial fibrillation by enhancing Ito (PMID:23280837, PMID:23280838, PMID:25854634, PMID:31293010, PMID:21349352, PMID:31173922, PMID:23400760). In neurons, Kv4.3 underlies subthreshold membrane potential oscillations in hippocampal interneurons and A-type currents in nociceptive trigeminal neurons whose downregulation drives neuropathic cold hypersensitivity (PMID:17314290, PMID:33472822, PMID:29313436).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Establishing the molecular identity of cardiac Ito was the foundational question; demonstrating that heterologous Kv4.3 reproduces the biophysics and pharmacology of native Ito identified the pore-forming subunit of this repolarizing current.

    Evidence Heterologous expression in oocytes/HEK with patch clamp and in situ hybridization across canine, human, and rat heart

    PMID:8831489

    Open questions at the time
    • Did not address auxiliary subunit requirements for native current
    • Human-specific complex composition not resolved
  2. 1999 High

    Whether tissue-specific Kv4.3 isoforms differ functionally was unknown; cloning long and short variants showed a 19-amino-acid insertion shifts inactivation voltage dependence, explaining tissue-specific gating and window current differences.

    Evidence RT-PCR cloning and heterologous expression with patch clamp in oocytes and HEK cells (rat and human)

    PMID:10200233 PMID:9450548

    Open questions at the time
    • Physiological consequence of isoform choice in vivo not established at this stage
    • Regulatory basis of tissue-specific splicing unknown
  3. 2002 High

    How native Ito kinetics arise from Kv4.3 alone was unresolved; KChIP2 subunits were shown to increase current density and tune inactivation/recovery in Ca2+-dependent and splice-variant-specific ways, with palmitoylation controlling membrane localization.

    Evidence Co-expression with KChIP2 isoforms, metabolic labeling for palmitoylation, mutagenesis, confocal imaging, and patch clamp

    PMID:12006572 PMID:12135940 PMID:12433945

    Open questions at the time
    • Stoichiometry of the channel-KChIP complex not defined
    • Structural basis of the interaction not yet resolved
  4. 2000 High

    Whether Ito causally controls cardiac repolarization in vivo was untested; gain- and loss-of-function gene transfer demonstrated that Kv4.3-mediated Ito sets plateau potential and APD and modulates QT.

    Evidence In vivo adenoviral Kv4.3 overexpression and dominant-negative W362F transfer with myocyte patch clamp and ECG

    PMID:10772652

    Open questions at the time
    • Species-specific Ito subunit dependence not addressed
    • Link to hypertrophy not yet made
  5. 2001 High

    The mechanism of Kv4.3 downregulation in hypertrophy was unknown; Ang II and phenylephrine were shown to act through distinct pathways — mRNA destabilization versus promoter suppression respectively.

    Evidence RNase protection, mRNA turnover, and promoter-reporter assays in neonatal rat cardiac myocytes

    PMID:11249870

    Open questions at the time
    • Identity of the mRNA-destabilizing factor not yet known
    • Promoter elements targeted by PE not mapped
  6. 2004 High

    How Kv4.3 gating is regulated by signaling was open; CaMKII was shown to directly phosphorylate S550 to slow inactivation and accelerate recovery, while AT1R was found to physically complex with Kv4.3 and mediate Ang II-induced internalization.

    Evidence Site-directed mutagenesis with CaMKII dialysis/inhibitory peptides; co-IP from canine ventricle plus FRET and patch clamp

    PMID:15342638 PMID:15456698

    Open questions at the time
    • Phosphatase counter-regulation not defined
    • Trafficking machinery of AT1R-driven internalization unresolved
  7. 2005 High

    What additional subunits reconstitute native human Ito was unresolved; DPPX/DPP6 was shown to be required, and combined with KChIP2a yields current matching native human ventricular Ito, with DPP6 protein present in human but not rat ventricle.

    Evidence qRT-PCR, Western blot, CHO co-expression, and patch clamp comparison to native human Ito

    PMID:15890703

    Open questions at the time
    • Full subunit stoichiometry of the native complex not resolved
    • Species differences in complex composition incompletely mapped
  8. 2006 High

    The molecular effector destabilizing Kv4.3 mRNA and the role of Kv4.3 as a CaMKII scaffold were defined; AUF1 acting on a 3'UTR ARE downstream of AT1R/NADPH-oxidase/p38 mediates mRNA decay, and Kv4.3 basally binds CaMKII to concentrate it at the membrane.

    Evidence 3'UTR reporter/mutagenesis with AUF1 overexpression/knockdown and RNA pull-down; co-IP from ventricular myocytes with patch clamp

    PMID:16556864 PMID:16648177 PMID:18789946

    Open questions at the time
    • In vivo contribution of AUF1 to disease remodeling not established
    • Dynamic regulation of CaMKII sequestration not fully resolved
  9. 2007 High

    Whether Kv4.3 is essential for native A-type currents was tested genetically; Kv4.3 knockout did not eliminate mouse ventricular Ito,f but selectively contributes to neuronal A-type currents underlying subthreshold oscillations.

    Evidence Kv4.3-/- mice with patch clamp and biochemistry; siRNA knockdown in hippocampal interneurons in acute slices

    PMID:17314290 PMID:18045613

    Open questions at the time
    • Functional redundancy with Kv4.2 in heart not fully dissected
    • Neuronal versus cardiac subunit dependence differs and is incompletely explained
  10. 2008 High

    The structural basis of KChIP modulation was unknown; the KChIP4a crystal structure with competitive Kv4.3 N-terminal peptide binding revealed a released KChIP N-terminus acting as a slow inactivation gate.

    Evidence X-ray crystallography (3.0 Å), competition binding, and chimeric channel electrophysiology

    PMID:19109250

    Open questions at the time
    • Full assembled channel-KChIP structure not solved
    • Generalizability across all KChIP isoforms not established
  11. 2009 High

    Multiple layers of Kv4.3 regulation were dissected: isoform-specific PKC modulation via T504 and PKCα-dependent current reduction, divergent thyroid-hormone-receptor transcriptional control, additional subunits (KCNE2, DPP10), toxin binding sites, and NRSF-mediated epigenetic silencing after nerve injury.

    Evidence Mutagenesis with PKC application, promoter-reporter/deletion mapping, co-expression electrophysiology, alanine scanning, and ChIP with NRSF knockdown

    PMID:16738002 PMID:19171649 PMID:19357248 PMID:19675305 PMID:20006971 PMID:20042375 PMID:20044444 PMID:21803046

    Open questions at the time
    • Integration of competing transcriptional inputs in vivo unclear
    • Crosstalk among the multiple regulatory pathways not modeled
  12. 2010 High

    The functional consequence of the Kv4.3-CaMKII complex and the neuronal subunit hierarchy were clarified; Kv4.3 binds CaMKII calmodulin sites to suppress its autophosphorylation and L-type Ca2+ current facilitation, and genetic dissection placed Kv4.3 alongside Kv4.2 and Kv1.4 as distinct IA components.

    Evidence Co-IP/FRET and patch clamp in cardiomyocytes; single/double knockout mice with cortical neuron patch clamp

    PMID:20371829 PMID:21148163

    Open questions at the time
    • Stoichiometry of CaMKII sequestration in vivo not quantified
    • Relative neuronal subunit contributions vary by cell type
  13. 2012 High

    The disease genetics of KCND3 were established; loss-of-function mutations cause SCA19/22 via ER retention and protein instability, while distinct gain-of-function mutations enhance Ito to cause Brugada syndrome and arrhythmias.

    Evidence Exome/Sanger sequencing, heterologous expression with localization and patch clamp, autopsy immunohistochemistry, and AP simulation

    PMID:21349352 PMID:22023388 PMID:23280837 PMID:23280838

    Open questions at the time
    • Genotype-phenotype correlations across mutation spectrum incomplete
    • Mechanism of ER quality-control recognition not defined
  14. 2015 High

    How loss-of-function mutants affect wild-type channels was unresolved; SCA19/22 mutants exert dominant-negative suppression of WT Kv4.3 trafficking and gating, with KChIP2 partially rescuing, and a voltage-sensor RVF duplication shows extra S4 charge profoundly impairs gating.

    Evidence Mutant/WT co-expression with surface expression and patch clamp plus KChIP2 rescue; exome sequencing with electrophysiology

    PMID:25854634 PMID:26189493

    Open questions at the time
    • In vivo dominant-negative penetrance in patients not quantified
    • Whether KChIP2 rescue is therapeutically achievable unknown
  15. 2014 High

    Endogenous and pharmacological modulators of Kv4.3 were identified; SEMA3A acts as a direct protein inhibitor whose disease mutations cause Kv4.3 gain-of-function, and NS5806 enhances current via Ca2+-dependent KChIP3 binding.

    Evidence Co-IP, domain-disruption mutagenesis, iPSC-CM assays, and biophysical binding (ITC/fluorescence) with mutagenesis

    PMID:24963029 PMID:25228688

    Open questions at the time
    • Physiological setting of SEMA3A-Kv4.3 regulation not fully defined
    • In vivo efficacy of small-molecule modulators not established
  16. 2022 High

    Translating Kv4.3 mechanism to precision therapy was the goal; patient-derived and isogenic iPSC-CM models confirmed gain-of-function mutations and demonstrated that channel blockers (acacetin, quinidine) normalize Ito and the action potential notch.

    Evidence Mutagenesis, heterologous and patient/isogenic iPSC-CM patch clamp and multielectrode array with pharmacology

    PMID:23400760 PMID:29313436 PMID:31173922 PMID:31293010 PMID:35861988

    Open questions at the time
    • Clinical efficacy of these blockers across mutation classes untested
    • Long-term safety of Ito-targeted therapy unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple, often opposing regulatory inputs (phosphorylation, subunit composition, receptor coupling, transcriptional and post-transcriptional control) are integrated to set Kv4.3 surface density and gating in specific cardiac and neuronal cell types in vivo remains unresolved.
  • No unified quantitative model of complex assembly and regulation
  • Cell-type-specific subunit/regulator combinations incompletely mapped
  • In vivo therapeutic targeting not validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0060089 molecular transducer activity 3 GO:0140313 molecular sequestering activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-112316 Neuronal System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-397014 Muscle contraction 2
Partners
AGTR1CAMK2DPP10DPP6KCNAB2KCNE2KCNIP2SEMA3A
Complex memberships
Kv4.3-AT1R complexKv4.3-CaMKII membrane complexKv4.3-KChIP-DPP6/DPPX native cardiac Ito complexKv4.3-KChIP2 channel complex

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Kv4.3 (KCND3) encodes a rapidly inactivating A-type K+ current with biophysical and pharmacological properties matching the native cardiac transient outward current (Ito) in canine ventricular myocytes, establishing Kv4.3 as the primary molecular correlate of Ito in canine and likely human heart. Heterologous expression in Xenopus oocytes and HEK cells, whole-cell patch clamp, in situ hybridization in canine, human, and rat heart Circulation research High 8831489
1997 A novel alternatively spliced variant of Kv4.3 with a 19-amino acid insertion in the C-terminal intracellular region was cloned from rat vas deferens; this longer isoform is the predominant form in rat heart and smooth muscle, whereas the previously reported shorter form predominates in brain. RT-PCR cloning from rat vas deferens, functional expression in HEK293 cells, whole-cell patch clamp FEBS letters High 9450548
1999 Two human Kv4.3 isoforms (long and short, differing by a 19-amino acid sequence) were cloned and expressed; both produce A-type K+ currents in Xenopus oocytes, and the short isoform has its steady-state inactivation curve shifted ~10 mV positive relative to the long isoform, shifting the window current peak accordingly. RT-PCR cloning, heterologous expression in Xenopus oocytes, whole-cell patch clamp Journal of neurophysiology High 10200233
2000 Kvβ2 subunits co-associate with Kv4.3 proteins in the brain (co-immunoprecipitation). Kvβ1 or Kvβ2 expression increases Kv4.3 current density and protein expression without affecting channel gating. This association requires the C-terminus but not the N-terminus of Kv4.3, indicating a novel interaction mode distinct from Kv1-family channels. Co-immunoprecipitation from rat brain, co-expression in HEK cells, whole-cell patch clamp, Western blot The Journal of biological chemistry High 11087728
2000 In vivo adenoviral overexpression of Kv4.3 in guinea pig myocytes generates robust transient outward current that progressively depresses the plateau potential and abbreviates action potential duration (APD). Dominant-negative Kv4.3-W362F suppressed Ito in rat ventriculocytes, prolonged APD ~30%, and extended the QT interval, demonstrating that Ito plays a causal role in setting plateau potential and APD. In vivo intramyocardial adenoviral gene transfer, whole-cell patch clamp in isolated myocytes, surface ECG recording The Journal of clinical investigation High 10772652
2000 Nicotine potently blocks Kv4.3 channels (IC50 ~40 nM) via both tonic (40%) and use-dependent (60%) block. Single-channel analysis showed reduced conductance, open probability, and open time with increased closed time. Nicotine does not act through neurotransmitter receptors, indicating direct channel block. Whole-cell and single-channel patch clamp in Xenopus oocytes expressing Kv4.3, canine ventricular myocyte Ito recordings, pharmacological receptor antagonist experiments Circulation High 10973847
2001 Angiotensin II (Ang II) downregulates Kv4.3 mRNA and protein by destabilizing the mRNA (accelerating degradation) without affecting transcription, whereas phenylephrine (PE) downregulates Kv4.3 by inhibiting promoter activity (transcriptional suppression), demonstrating two independent mechanisms for Kv4.3 downregulation in cardiac hypertrophy. RNase protection assays, immunoblot, mRNA turnover measurements, Kv4.3 5'-flanking region cloning and promoter-reporter assays in neonatal rat cardiac myocytes Circulation research High 11249870
2002 KChIP2 splice variants (KChIP2S, KChIP2T, and a previously described isoform) each increase Kv4.3 current density, slow inactivation in a Ca2+-dependent manner, and hasten recovery from inactivation in a splice-variant-specific fashion. KChIP2 expression is graded transmurally in human and canine left ventricle. Kinetic RT-PCR, Western blot, immunocytochemistry, whole-cell patch clamp with co-expression in heterologous cells Circulation High 12135940
2002 KChIP2 palmitoylation at N-terminal cysteines is required for efficient plasma membrane localization of Kv4.3 channels. Longer KChIP2 isoforms containing a 32-amino acid N-terminal peptide with palmitoylation sites produce larger increases in Kv4.3 protein level and current density; mutating these cysteines reduces membrane localization and current enhancement. Metabolic labeling for palmitoylation, mutagenesis of palmitoylation cysteines, confocal immunofluorescence, whole-cell patch clamp in heterologous cells The Journal of biological chemistry High 12006572
2002 A structurally minimal KChIP2 isoform (KChIP2d, C-terminal 70 amino acids with one EF-hand) is sufficient to accelerate Kv4.3 recovery from inactivation and slow inactivation kinetics. The EF-hand modulates inactivation but not recovery; Ca2+-independent recovery effects map to a stretch of amino acids outside the EF-hand. Cloning of KChIP2d from ferret heart, co-expression with Kv4.3 in Xenopus oocytes, whole-cell patch clamp, mutagenesis of EF-hand The Journal of physiology High 12433945
2002 Kv4.3 exhibits C-type (outer pore collapse) inactivation: removal of external K+ accelerates inactivation and promotes cumulative inactivation by repetitive stimulation. This is consistent with K+ occupancy of a selectivity filter site that stabilizes the conducting state. Whole-cell voltage-clamp with varied external K+ concentrations and ion substitution experiments in HEK cells expressing Kv4.3 The Journal of membrane biology Medium 12172648
2004 CaMKII directly phosphorylates Kv4.3 at S550 in the C-terminal region, slowing inactivation and accelerating recovery from inactivation. The S550A mutation renders Kv4.3 insensitive to both CaMKII dialysis and CaMKII inhibitory peptide, identifying S550 as the functionally critical phosphorylation site. Whole-cell patch clamp with intrapipette delivery of autothiophosphorylated CaMKII or inhibitory peptides, site-directed mutagenesis of consensus CaMKII phosphorylation sites in Kv4.3 American journal of physiology. Cell physiology High 15456698
2004 Angiotensin receptor type 1 (AT1R) forms a physical complex with Kv4.3: co-immunoprecipitation from canine ventricle and from HEK293 cells co-expressing AT1R, Kv4.3, and KChIP2. FRET demonstrates close spatial proximity. Ang II stimulation internalizes Kv4.3 together with AT1R and shifts activation voltage threshold of remaining surface Kv4.3 to more positive values. Co-immunoprecipitation from native canine ventricle and HEK293 cells, FRET with CFP/YFP-tagged proteins, live-cell confocal imaging, whole-cell patch clamp The Journal of biological chemistry High 15342638
2004 KChIP2b and KChIP2d modulate Kv4.3 gating by accelerating recovery from inactivation (acting on closed-state inactivation transitions), slowing closed-state inactivation, and promoting open-state inactivation. Ca2+-dependent effects on inactivation are mediated through open-state (not closed-state) inactivation mechanisms. Kinetic analysis of macroscopic currents in Xenopus oocytes co-expressing Kv4.3 with KChIP2 isoforms, multi-state kinetic modeling The Journal of physiology High 14724186
2004 In vivo adenoviral Kv4.3 gene transfer in rats subjected to aortic stenosis increased Ito density, shortened APD50, and abrogated cardiac hypertrophy. This was associated with significant reductions in calcineurin and NFATc1 expression, linking Kv4.3-mediated Ito to the calcineurin/NFAT hypertrophic pathway. In vivo adenoviral gene transfer, whole-cell patch clamp, immunoblot for calcineurin and NFATc1, heart weight/body weight ratio, cellular capacitance measurements Circulation High 15557376
2005 DPPX (DPP6) co-expressed with Kv4.3 in CHO cells accelerates inactivation and recovery from inactivation; co-expression of DPPX together with KChIP2a and Kv4.3 produces current kinetics matching native human ventricular Ito. DPPX protein is detected in human but not rat ventricle by specific antibody, establishing it as an essential component of the native human cardiac Ito channel complex. Quantitative real-time RT-PCR, Western blot, co-expression in CHO cells, whole-cell patch clamp comparison to native human ventricular Ito The Journal of physiology High 15890703
2006 Ang II activates AT1 receptors to destabilize Kv4.3 channel mRNA via the 3'UTR through NADPH oxidase-derived superoxide acting on the ASK1-p38 kinase pathway. Mechanical stretch also downregulates Kv4.3 3'UTR reporter activity requiring AT1 receptors and NADPH oxidase. The effect is specific: Kv4.2 and Kv1.5 3'-UTR sequences are insensitive to Ang II. 3'UTR-reporter mRNA and activity assays in neonatal rat ventricular myocytes, dominant-negative rac, NADPH oxidase inhibitors, SOD/catalase overexpression, ASK1-p38 pathway inhibitors, stretch experiments Circulation research High 16556864
2006 CaMKII co-immunoprecipitates with Kv4.3 channels in rat ventricular myocytes without requiring Ca2+ elevation (basal association), whereas CaMKII association with Kv4.2 requires Ca2+ increase. Inhibition of CaMKII specifically accelerates Kv4.3 inactivation. Kv4.3 thus serves as a molecular scaffold concentrating CaMKII at the membrane, allowing localized Ca2+-dependent regulation of associated Kv4.2 channels. Co-immunoprecipitation from rat ventricular myocytes, Western blot phosphorylation analysis, whole-cell patch clamp with CaMKII inhibitors in HEK cells transfected with Kv4.2 or Kv4.3 American journal of physiology. Heart and circulatory physiology High 16648177
2006 DPP10, another dipeptidyl peptidase-related subunit, modulates Kv4.3 inactivation primarily by affecting closed-state inactivation and causing negative shifts in steady-state activation and inactivation. When co-expressed with both Kv4.3 and KChIP2b, the effects of DPP10 on steady-state properties are abolished, while closed-state inactivation differences remain, demonstrating that DPP10 and KChIP2b modulate distinct inactivation states. Heterologous co-expression in CHO or HEK cells, whole-cell patch clamp, comparison of Kv4.3 alone, Kv4.3+KChIP2b, Kv4.3+DPP10, and triple combinations; truncation mutant of DPP10 American journal of physiology. Cell physiology High 16738002
2007 Kv4.3 mediates A-type K+ currents underlying subthreshold membrane potential oscillations (MPOs) in hippocampal CA1 LM/RAD interneurons. siRNA knockdown of Kv4.3 selectively impaired A-type K+ currents and abolished MPOs in these specific interneuron subpopulations. siRNA knockdown, whole-cell patch clamp in hippocampal interneurons in acute slices, immunocytochemistry for Kv4.3 The Journal of neuroscience High 17314290
2007 Genetic deletion of Kv4.3 (KCND3-/-) in mice does not eliminate ventricular Ito,f: functional Ito,f channels are expressed at normal density in Kv4.3-/- myocytes with unchanged properties, indicating Kv4.3 is not required for mouse ventricular Ito,f channel generation (in contrast to Kv4.2). Targeted gene disruption (Kv4.3-/- mice), whole-cell voltage clamp, quantitative RT-PCR, Western blot Journal of molecular and cellular cardiology High 18045613
2008 KChIP4a has a crystal structure (3.0 Å resolution) showing distinct N-terminal α-helices. Competitive binding of the Kv4.3 N-terminal peptide to the hydrophobic groove of KChIP4a core displaces the KChIP4a N-terminus; this released N-terminus serves as a slow inactivation gate for Kv4.3. The first N-terminal α-helix of KChIP4a (residues 1–34) is sufficient to confer slow inactivation when fused to N-terminally truncated Kv4.3. X-ray crystallography (3.0 Å), biochemical competition binding, electrophysiology with N-terminal peptide application and chimeric channel constructs The Journal of biological chemistry High 19109250
2008 AUF1 (ARE/poly-(U)-binding/degradation factor 1) is upregulated by Ang II through AT1R-NADPH oxidase-p38 MAPK signaling. Elevated AUF1 binds to an AU-rich element (ARE) in the Kv4.3 3'UTR, destabilizing the mRNA. AUF1 overexpression mimics the Ang II effect, AUF1 siRNA blocks it, and pull-down assays confirm increased AUF1 binding to the Kv4.3 ARE after Ang II treatment. 3'UTR deletion and mutagenesis analysis, AUF1 overexpression and siRNA knockdown, RNA pull-down assays, reporter mRNA stability assays in neonatal rat ventricular myocytes Journal of molecular and cellular cardiology High 18789946
2009 NRSF (neuron-restrictive silencer factor) binds directly to the NRSE in the Kv4.3 gene promoter after peripheral nerve injury, causing epigenetic silencing: ChIP assay shows increased NRSF binding and markedly reduced acetylation of histone H4 (but not H3) at the Kv4.3-NRSE in dorsal root ganglion. Antisense knockdown of NRSF blocks the injury-induced Kv4.3 downregulation. Chromatin immunoprecipitation (ChIP) for NRSF binding and histone acetylation, antisense NRSF knockdown in rat dorsal root ganglion after sciatic nerve injury, RT-PCR Neuroscience High 20006971
2009 KCNE2 co-expression with Kv4.3 reduces peak current density, slows inactivation, and causes a positive shift of steady-state inactivation, rendering Kv4.3 more similar to native cardiac Ito. KCNE2 variants M54T and I57T produce gain-of-function effects (increased current density, slowed inactivation, faster recovery) compared to wild-type KCNE2. Co-expression of Kv4.3 with KCNE2 WT or variants in heterologous cells, whole-cell patch clamp Heart rhythm Medium 20042375
2009 The S3b region of Kv4.3 (residues L275 and V276) constitutes the binding site for the gating modifier toxin HpTx2; alanine scanning shows that simultaneous mutation of L275A and V276A nearly eliminates toxin interaction. KChIP2b co-expression increases HpTx2 affinity for Kv4.3, attributed to KChIP2b-induced stabilization of the closed state. Alanine-scanning mutagenesis of Kv4.3 S3b, electrophysiological concentration-response analysis in Xenopus oocytes, KChIP2b co-expression Molecular pharmacology High 19357248
2009 PKC isoform-specific regulation: PKCα plays the central role in PKC-dependent downregulation of Kv4.3 current. PMA and conventional PKC activator TMX reduced Kv4.3 current; these effects were abolished by PKCα inhibition (HBDDE) or PKCα siRNA but not by PKCβ inhibition or siRNA. PKCα activator iripallidal mimicked the effect on Kv4.3. Xenopus oocyte two-electrode voltage clamp, PKC isoform-selective inhibitors/activators, siRNA knockdown of PKCα vs PKCβ, native rat cardiomyocyte patch clamp Journal of molecular and cellular cardiology High 21803046
2009 Closed-state inactivation (CSI) of Kv4.3 is differentially regulated by PKC in the two splice isoforms. PMA (PKC activator) reduces CSI magnitude in Kv4.3-short but increases CSI in Kv4.3-long. This isoform-specific difference maps to T504, a PKC phosphorylation site unique to the long isoform; T504D mutation eliminates the PMA response. Xenopus oocyte expression, whole-cell voltage clamp, PMA and purified PKC application, site-directed mutagenesis of T504 American journal of physiology. Cell physiology High 19675305
2010 A dynamic Kv4.3-CaMKII complex is present at the plasma membrane of cardiomyocytes (co-IP and FRET). CaMKII dissociation from this complex increases CaMKII autophosphorylation and L-type Ca2+ current facilitation. Kv4.3 overexpression reduces basal CaMKII autophosphorylation and eliminates Ca2+-induced CaMKII activation by binding to the calmodulin binding sites of CaMKII. Co-immunoprecipitation from cardiomyocytes, FRET (CFP/YFP), overexpression of Kv4.3, BAPTA vs EGTA Ca2+ chelation, whole-cell patch clamp for L-type Ca2+ current European heart journal High 21148163
2010 Kv4.2 and Kv4.3, along with Kv1.4, encode distinct components of the macroscopic IA in mouse cortical pyramidal neurons. Genetic deletion of Kv4.2 and Kv4.3 (double knockout) reveals a residual Kv1.4-encoded component; Kv4.3 encodes the larger component in neurons lacking both Kv4.2 and Kv1.4, and deletion of individual subunits causes subunit-specific electrical remodeling. Single and double knockout mouse models (Kv4.2-/-, Kv4.3-/-, Kv4.2-/-/Kv4.3-/-), whole-cell patch clamp in cortical pyramidal neurons, 4-AP pharmacology The Journal of neuroscience High 20371829
2011 Nitric oxide (NO) inhibits Kv4.3 current (IC50 ~375 nM) through activation of adenylate cyclase → cAMP-dependent protein kinase (PKA) → serine-threonine phosphatase 2A signaling cascade. This inhibition prolongs the plateau of mouse atrial action potential. Whole-cell patch clamp in CHO cells expressing Kv4.3 and in isolated human atrial and mouse ventricular myocytes, NO donors, adenylate cyclase and PKA modulators, phosphatase inhibitors Cardiovascular research Medium 18678642
2011 KCND3 gain-of-function mutations L450F and G600R (found in Brugada syndrome patients) increase peak Ito current density by 146% and 50% respectively when co-expressed with KChIP2 in HEK293 cells, establishing a gain-of-function mechanism for these mutations in Brugada syndrome pathogenesis. Site-directed mutagenesis, co-expression with KChIP2 in HEK293 cells, whole-cell patch clamp, Luo-Rudy AP model simulation Heart rhythm High 21349352
2012 KCND3 mutations cause SCA19/22: p.F227del mutant Kv4.3 is retained in the cytoplasm (loss of plasma membrane localization) with absent A-type K+ channel conductance in patch clamp. p.G345V and p.T377M mutations also identified as pathogenic, confirming KCND3 as the SCA19/22 gene across multiple ethnic groups. Whole exome sequencing, Sanger sequencing, immunofluorescence localization in heterologous cells, whole-cell patch clamp Annals of neurology High 23280837
2012 SCA19 (KCND3) mutations T352P, M373I, and S390N cause Kv4.3 retention in the endoplasmic reticulum and enhanced protein instability. KChIP2 rescues membrane localization and stability of two of three mutants but does not fully restore channel function. T352P Purkinje cells show intracellular Kv4.3 accumulation with reduced protein levels in autopsy material. Exome sequencing, HeLa cell ectopic expression, immunofluorescence, whole-cell patch clamp, SCA19 cerebellar autopsy immunohistochemistry, KChIP2 rescue co-expression Annals of neurology High 23280838
2013 KCND3 gain-of-function mutation A545P in Kv4.3 (found in early-onset lone AF patient) increases peak current density and slows inactivation compared to WT, both in the absence and presence of KChIP2, constituting a gain-of-function associated with atrial fibrillation. Direct sequencing of KCND3 in AF patients, co-expression in CHO-K1 cells with or without KChIP2, whole-cell patch clamp Cardiovascular research Medium 23400760
2014 SEMA3A (semaphorin 3A) is a naturally occurring protein inhibitor that selectively reduces Kv4.3 peak current density without altering cell surface expression. Co-immunoprecipitation and disruption of a hanatoxin-like binding domain on Kv4.3 indicate a direct protein-protein interaction. SEMA3A mutations found in Brugada syndrome disrupt SEMA3A's ability to inhibit Kv4.3, resulting in gain-of-function. Co-expression in HEK293 cells with whole-cell patch clamp, co-immunoprecipitation, disruption of putative toxin-binding domain on Kv4.3, SEMA3A perfusion, iPSC-cardiomyocyte assays Circulation research High 24963029
2014 NS5806 (Kv4.3 current activator) binds at a hydrophobic site on the C-terminus of KChIP3 in a Ca2+-dependent manner (Kd 2–5 µM in Ca2+-bound form). NS5806 increases affinity between KChIP3 and the N-terminus of Kv4.3 and decreases the dissociation rate. Tyr-174 and Phe-218 on KChIP3 are required for this enhancement. Fluorescence spectroscopy, isothermal calorimetry, docking simulations, mutagenesis of KChIP3 residues The Journal of biological chemistry High 25228688
2015 SCA19/22-mutant Kv4.3 subunits exert a dominant-negative effect on WT Kv4.3 trafficking and surface expression in the absence of KChIP2; KChIP2 can rescue this dominant-negative effect. All SCA19/22 mutants either suppress WT Kv4.3 current amplitude or alter channel gating in a dominant manner. Co-expression of mutant and WT Kv4.3 in heterologous cells, surface expression assays, whole-cell patch clamp, KChIP2 rescue co-expression Cellular and molecular life sciences High 25854634
2015 A de novo KCND3 mutation (p.Arg293_Phe295dup) duplicating the RVF motif in the voltage-sensor domain causes a severe shift of voltage-dependence of gating to more depolarized voltages, demonstrating that addition of an extra positive charge to the S4 voltage sensor profoundly impairs Kv4.3 channel function. Whole exome sequencing, immunocytochemistry, immunoblot, whole-cell patch clamp BMC medical genetics Medium 26189493
2009 Ang II acting via AT1R-ROS-p38 MAPK signaling downregulates Kv4.3 mRNA and protein expression and decreases A-type K+ current in CATH.a neurons. This mechanism contributes to Kv4.3 downregulation in the RVLM of chronic heart failure rats, leading to neuronal hyperexcitability and sympathoexcitation. Rat Genome GeneChip array, real-time RT-PCR, Western blot, whole-cell patch clamp in CATH.a cells, Tempol (superoxide scavenger) and SB-203580 (p38 inhibitor) pharmacology, RVLM microinjection of 4-AP American journal of physiology. Heart and circulatory physiology Medium 20044444
2009 Thyroid hormone receptors TRα1 and TRβ1 divergently regulate KCND3 transcription: TRα1 activates and TRβ1 suppresses KCND3 promoter activity. Deletion and mutagenesis mapping identified the TRα1 response element at −1651 bp (G-1651T abolishes activation) and the TRβ1 response element at −73 bp (G-73T abolishes suppression) of the KCND3 transcription start site. Adenoviral overexpression of TRα1/TRβ1 in rat cardiomyocytes, KCND3 5'-flanking reporter constructs, deletion analysis, site-directed mutagenesis of TR binding sites, patch clamp The Journal of physiology High 19171649
2012 Large T-antigen increases Kv4.3 expression through upregulation of transcription factor Sp1; Sp1 decoy oligonucleotide reduces Kv4.3 expression in HEK-293T cells, and Sp1 overexpression increases Kv4.3 in HEK-293 cells. Inhibition of Kv4.3 (by 4-AP or siRNA) induces cell apoptosis and necrosis that is rescued by the CaMKII inhibitor KN-93, placing Kv4.3 upstream of CaMKII-mediated cell death. Sp1 decoy oligonucleotide, Sp1 overexpression vector, siRNA knockdown of Kv4.3, 4-AP pharmacology, cell viability/death assays, KN-93 rescue The Biochemical journal Medium 22023388
2018 Kv4.3 expression in nociceptive-like TG neurons is downregulated following infraorbital nerve chronic constrictive injury (ION-CCI), reducing IA currents and increasing neuronal excitability. Pharmacological inhibition of Kv4.3 with phrixotoxin-2 reproduced cold hypersensitivity; pharmacological potentiation of Kv4.3 amplified IA and alleviated cold hypersensitivity. Immunostaining, whole-cell patch clamp in dissociated TG neurons, orofacial operant behavioral test, phrixotoxin-2 injection and Kv4.3 activator application in ION-CCI rats The Journal of neuroscience High 29313436 33472822
2019 Novel SCA19/22-associated KCND3 mutations (C317Y, P375S, V338E, T377M) all exhibit loss-of-function phenotypes: reduced current amplitudes, enhanced protein degradation, and defective membrane trafficking in heterologous expression. Co-expression of mutant and WT Kv4.3 demonstrates dominant-negative effects on protein biosynthesis and voltage-dependent gating of WT channels. In vitro heterologous expression, whole-cell patch clamp, protein biochemistry (Western blot for degradation), immunofluorescence for membrane trafficking, co-expression of mutant+WT Human mutation High 31293010
2019 De novo KCND3 mutation G306A (Gly306Ala) associated with early repolarization syndrome produces gain-of-function: increased current density, slow inactivation, and slow recovery from inactivation compared to WT. Quinidine restores inactivation kinetics of mutant Kv4.3, consistent with its clinical efficacy in the patient. Whole exome sequencing, whole-cell patch clamp in cultured cells, action potential simulation Heart rhythm Medium 31173922
2020 Alternative isoforms of Kv4 auxiliary subunits (KChIP1 vs KChIP4e and DPP6S) expressed in different CCK+ interneurons determine their firing phenotype. Neurons expressing KChIP4e and DPP6S with Kv4.3 display distinct low-voltage-activated K+ currents and a previously undetected membrane potential-dependent firing phenotype, while neurons with KChIP1 fire regularly, demonstrating that auxiliary subunit isoform identity specifies neuronal excitability. Whole-cell patch clamp in rat hippocampal CA3 slices, single-cell transcriptomics (gene profiling), immunofluorescence, pharmacology eLife Medium 32490811
2021 The miR-27a-3p/Hoxa10/Kv4.3 axis mediates Ang II-induced cardiomyocyte hypertrophy: miR-27a-3p targets the 3'UTR of Hoxa10 (confirmed by luciferase assay), reducing Hoxa10 protein; Hoxa10 overexpression reverses hypertrophy and electrical remodeling and positively regulates Kv4.3 expression. Ang II-induced cardiomyocyte hypertrophy model, luciferase reporter assay for miR-27a-3p targeting of Hoxa10 3'UTR, miR-27a-3p inhibitor, Hoxa10 overexpression, Western blot, RT-PCR Frontiers in pharmacology Medium 34248630
2022 Acacetin (natural flavone) inhibits KCND3-encoded Kv4.3 WT with IC50 of 7.2 µM. KCND3-V392I gain-of-function mutation increases Ito by 92% in HEK cells and 61% in patient-derived iPSC-CMs; 30 µM acacetin inhibited V392I peak Ito by 96% and abolished the accentuated action potential notch in V392I iPSC-CMs. Site-directed mutagenesis, whole-cell patch clamp in TSA201 cells, gene-edited isogenic and patient-specific iPSC-CMs with multielectrode array and patch clamp, Western blot, immunocytochemistry Circulation. Genomic and precision medicine High 35861988

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Role of the Kv4.3 K+ channel in ventricular muscle. A molecular correlate for the transient outward current. Circulation research 389 8831489
1998 Molecular basis of transient outward potassium current downregulation in human heart failure: a decrease in Kv4.3 mRNA correlates with a reduction in current density. Circulation 321 9760292
2011 Transient outward current (I(to)) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome. Heart rhythm 188 21349352
2012 Mutations in KCND3 cause spinocerebellar ataxia type 22. Annals of neurology 126 23280837
2002 Palmitoylation of KChIP splicing variants is required for efficient cell surface expression of Kv4.3 channels. The Journal of biological chemistry 116 12006572
2012 Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19. Annals of neurology 114 23280838
2005 Expression and function of dipeptidyl-aminopeptidase-like protein 6 as a putative beta-subunit of human cardiac transient outward current encoded by Kv4.3. The Journal of physiology 102 15890703
2002 Regulation of Kv4.3 current by KChIP2 splice variants: a component of native cardiac I(to)? Circulation 101 12135940
1997 Molecular cloning and tissue distribution of an alternatively spliced variant of an A-type K+ channel alpha-subunit, Kv4.3 in the rat. FEBS letters 101 9450548
2013 A novel KCND3 gain-of-function mutation associated with early-onset of persistent lone atrial fibrillation. Cardiovascular research 100 23400760
2000 Nicotine is a potent blocker of the cardiac A-type K(+) channels. Effects on cloned Kv4.3 channels and native transient outward current. Circulation 96 10973847
1997 Decreased expression of Kv4.2 and novel Kv4.3 K+ channel subunit mRNAs in ventricles of renovascular hypertensive rats. Circulation research 90 9314834
1999 Regional contributions of Kv1.4, Kv4.2, and Kv4.3 to transient outward K+ current in rat ventricle. The American journal of physiology 88 10330244
2009 Neuron-restrictive silencer factor causes epigenetic silencing of Kv4.3 gene after peripheral nerve injury. Neuroscience 86 20006971
2000 Molecular remodeling of Kv4.3 potassium channels in human atrial fibrillation. Journal of cardiovascular electrophysiology 82 10868735
2000 Kvbeta subunits increase expression of Kv4.3 channels by interacting with their C termini. The Journal of biological chemistry 80 11087728
2006 Differential expression of I(A) channel subunits Kv4.2 and Kv4.3 in mouse visual cortical neurons and synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 17122053
2004 Regulation of Kv4.3 currents by Ca2+/calmodulin-dependent protein kinase II. American journal of physiology. Cell physiology 68 15456698
2001 Independent regulation of cardiac Kv4.3 potassium channel expression by angiotensin II and phenylephrine. Circulation research 66 11249870
2002 Elucidating KChIP effects on Kv4.3 inactivation and recovery kinetics with a minimal KChIP2 isoform. The Journal of physiology 65 12433945
2006 Angiotensin II and stretch activate NADPH oxidase to destabilize cardiac Kv4.3 channel mRNA. Circulation research 64 16556864
2007 Kv4.3-mediated A-type K+ currents underlie rhythmic activity in hippocampal interneurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 17314290
2000 Molecular dissection of cardiac repolarization by in vivo Kv4.3 gene transfer. The Journal of clinical investigation 62 10772652
2003 A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23. Brain : a journal of neurology 60 12764052
2012 Novel mutations in the KCND3-encoded Kv4.3 K+ channel associated with autopsy-negative sudden unexplained death. Human mutation 59 22457051
2004 Regulation of Kv4.3 voltage-dependent gating kinetics by KChIP2 isoforms. The Journal of physiology 59 14724186
2004 Angiotensin receptor type 1 forms a complex with the transient outward potassium channel Kv4.3 and regulates its gating properties and intracellular localization. The Journal of biological chemistry 59 15342638
2010 Molecular dissection of I(A) in cortical pyramidal neurons reveals three distinct components encoded by Kv4.2, Kv4.3, and Kv1.4 alpha-subunits. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 20371829
1997 Cloning, expression and CNS distribution of Kv4.3, an A-type K+ channel alpha subunit. FEBS letters 55 9001401
2015 First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy. BMC medical genetics 51 26189493
2009 Downregulated Kv4.3 expression in the RVLM as a potential mechanism for sympathoexcitation in rats with chronic heart failure. American journal of physiology. Heart and circulatory physiology 51 20044444
2006 Differential modulation of Kv4.2 and Kv4.3 channels by calmodulin-dependent protein kinase II in rat cardiac myocytes. American journal of physiology. Heart and circulatory physiology 50 16648177
2002 Identification of a novel SCA locus ( SCA19) in a Dutch autosomal dominant cerebellar ataxia family on chromosome region 1p21-q21. Human genetics 50 12384780
2004 In vivo cardiac gene transfer of Kv4.3 abrogates the hypertrophic response in rats after aortic stenosis. Circulation 49 15557376
2014 Characterization of SEMA3A-encoded semaphorin as a naturally occurring Kv4.3 protein inhibitor and its contribution to Brugada syndrome. Circulation research 46 24963029
2007 Kv4.3 is not required for the generation of functional Ito,f channels in adult mouse ventricles. Journal of molecular and cellular cardiology 43 18045613
2008 Nitric oxide inhibits Kv4.3 and human cardiac transient outward potassium current (Ito1). Cardiovascular research 42 18678642
1999 Characterisation of Kv4.3 in HEK293 cells: comparison with the rat ventricular transient outward potassium current. Cardiovascular research 39 10325966
2019 A de novo gain-of-function KCND3 mutation in early repolarization syndrome. Heart rhythm 36 31173922
2018 Down-regulation of Kv4.3 channels and a-type K+ currents in V2 trigeminal ganglion neurons of rats following oxaliplatin treatment. Molecular pain 35 29313436
1999 Functional expression of an inactivating potassium channel (Kv4.3) in a mammalian cell line. Cardiovascular research 35 10325968
2019 Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: Identification of a new KCND3 phenotype and novel genes causing Dravet syndrome. Seizure 34 30776697
1999 Cloning and expression of the human kv4.3 potassium channel. Journal of neurophysiology 34 10200233
2003 Dihydropyridine Ca2+ channel antagonists and agonists block Kv4.2, Kv4.3 and Kv1.4 K+ channels expressed in HEK293 cells. British journal of pharmacology 33 12788813
2009 Endocannabinoids and cannabinoid analogues block human cardiac Kv4.3 channels in a receptor-independent manner. Journal of molecular and cellular cardiology 32 19616555
2003 Contrasting expression of Kv4.3, an A-type K+ channel, in migrating Purkinje cells and other post-migratory cerebellar neurons. The European journal of neuroscience 32 12911756
2014 Modulation of the voltage-gated potassium channel (Kv4.3) and the auxiliary protein (KChIP3) interactions by the current activator NS5806. The Journal of biological chemistry 31 25228688
2006 DPP10 is an inactivation modulatory protein of Kv4.3 and Kv1.4. American journal of physiology. Cell physiology 31 16738002
2019 Expression, Cellular and Subcellular Localisation of Kv4.2 and Kv4.3 Channels in the Rodent Hippocampus. International journal of molecular sciences 30 30634540
2002 Kinetic properties of Kv4.3 and their modulation by KChIP2b. Biochemical and biophysical research communications 30 12150935
1999 Blockade by N-3 polyunsaturated fatty acid of the Kv4.3 current stably expressed in Chinese hamster ovary cells. British journal of pharmacology 29 10433502
2010 Dynamic Kv4.3-CaMKII unit in heart: an intrinsic negative regulator for CaMKII activation. European heart journal 28 21148163
2021 Kv4.3 Channel Dysfunction Contributes to Trigeminal Neuropathic Pain Manifested with Orofacial Cold Hypersensitivity in Rats. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 33472822
2010 High-mobility group box 1 (HMGB1) downregulates cardiac transient outward potassium current (Ito) through downregulation of Kv4.2 and Kv4.3 channel transcripts and proteins. Journal of molecular and cellular cardiology 27 20483361
2008 Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation. The Journal of biological chemistry 27 19109250
2015 Spinocerebellar ataxia type 19/22 mutations alter heterocomplex Kv4.3 channel function and gating in a dominant manner. Cellular and molecular life sciences : CMLS 26 25854634
2011 Rosiglitazone inhibits Kv4.3 potassium channels by open-channel block and acceleration of closed-state inactivation. British journal of pharmacology 26 21232039
2005 Spironolactone and its main metabolite canrenoic acid block hKv1.5, Kv4.3 and Kv7.1 + minK channels. British journal of pharmacology 26 15980874
2010 Celecoxib blocks cardiac Kv1.5, Kv4.3 and Kv7.1 (KCNQ1) channels: effects on cardiac action potentials. Journal of molecular and cellular cardiology 25 20858500
2002 External pore collapse as an inactivation mechanism for Kv4.3 K+ channels. The Journal of membrane biology 25 12172648
2020 KCND3-Related Neurological Disorders: From Old to Emerging Clinical Phenotypes. International journal of molecular sciences 24 32823520
2017 Expanding the phenotype of SCA19/22: Parkinsonism, cognitive impairment and epilepsy. Parkinsonism & related disorders 24 28947073
2009 KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders. Heart rhythm 24 20042375
2012 Large T-antigen up-regulates Kv4.3 K⁺ channels through Sp1, and Kv4.3 K⁺ channels contribute to cell apoptosis and necrosis through activation of calcium/calmodulin-dependent protein kinase II. The Biochemical journal 23 22023388
2009 S3b amino acid substitutions and ancillary subunits alter the affinity of Heteropoda venatoria toxin 2 for Kv4.3. Molecular pharmacology 23 19357248
2008 Effects of MiRP1 and DPP6 beta-subunits on the blockade induced by flecainide of Kv4.3/KChIP2 channels. British journal of pharmacology 23 18536731
2004 Diltiazem inhibits hKv1.5 and Kv4.3 currents at therapeutic concentrations. Cardiovascular research 23 15537499
2014 The potential role of Kv4.3 K+ channel in heart hypertrophy. Channels (Austin, Tex.) 22 24762397
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
2005 Clinical, psychological, and genetic characteristics of spinocerebellar ataxia type 19 (SCA19). Cerebellum (London, England) 22 15895560
2006 Interaction of riluzole with the closed inactivated state of Kv4.3 channels. The Journal of pharmacology and experimental therapeutics 21 16815868
2003 Differential inhibition of transient outward currents of Kv1.4 and Kv4.3 by endothelin. Biochemical and biophysical research communications 21 14521958
2013 Inhibition of cardiac Kv1.5 and Kv4.3 potassium channels by the class Ia anti-arrhythmic ajmaline: mode of action. Naunyn-Schmiedeberg's archives of pharmacology 20 23832378
2010 KChIP1 modulation of Kv4.3-mediated A-type K(+) currents and repetitive firing in hippocampal interneurons. Neuroscience 20 21129448
2019 Novel SCA19/22-associated KCND3 mutations disrupt human KV 4.3 protein biosynthesis and channel gating. Human mutation 19 31293010
2001 Regional expression of the splice variants of Kv4.3 in rat brain and effects of C-terminus deletion on expressed K+ currents. Life sciences 19 11270617
2008 Enhanced trafficking of tetrameric Kv4.3 channels by KChIP1 clamping. Neurochemical research 18 18401705
2018 Novel De Novo KCND3 Mutation in a Japanese Patient with Intellectual Disability, Cerebellar Ataxia, Myoclonus, and Dystonia. Cerebellum (London, England) 17 28895081
2010 Inhibition of Kv4.3 by genistein via a tyrosine phosphorylation-independent mechanism. American journal of physiology. Cell physiology 17 21148405
2008 AUF1 is upregulated by angiotensin II to destabilize cardiac Kv4.3 channel mRNA. Journal of molecular and cellular cardiology 17 18789946
2019 KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern. JCI insight 16 31600170
2017 A novel KCND3 mutation associated with early-onset lone atrial fibrillation. Oncotarget 16 29383177
2015 Role of Kv4.3 in Vibration-Induced Muscle Pain in the Rat. The journal of pain 16 26721612
2017 Cardiotoxic effect of levofloxacin and ciprofloxacin in rats with/without acute myocardial infarction: Impact on cardiac rhythm and cardiac expression of Kv4.3, Kv1.2 and Nav1.5 channels. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 28544933
2015 Effects of neferine on Kv4.3 channels expressed in HEK293 cells and ex vivo electrophysiology of rabbit hearts. Acta pharmacologica Sinica 15 26592512
2013 Bone morphogenetic protein-4 contributes to the down-regulation of Kv4.3 K+ channels in pathological cardiac hypertrophy. Biochemical and biophysical research communications 15 23747723
2003 Extracellular acidosis modulates drug block of Kv4.3 currents by flecainide and quinidine. Journal of cardiovascular electrophysiology 15 12875427
2000 Genomic organisation and chromosomal localisation of two members of the KCND ion channel family, KCND2 and KCND3. Human genetics 15 10942109
2022 Acacetin, a Potent Transient Outward Current Blocker, May Be a Novel Therapeutic for KCND3-Encoded Kv4.3 Gain-of-Function-Associated J-Wave Syndromes. Circulation. Genomic and precision medicine 14 35861988
2021 MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression. Frontiers in pharmacology 14 34248630
2021 Rare Gain-of-Function KCND3 Variant Associated with Cerebellar Ataxia, Parkinsonism, Cognitive Dysfunction, and Brain Iron Accumulation. International journal of molecular sciences 14 34361012
2015 Analysis of SCA8, SCA10, SCA12, SCA17 and SCA19 in patients with unknown spinocerebellar ataxia: a Thai multicentre study. BMC neurology 14 26374734
2020 Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits. eLife 13 32490811
2018 Kv4.3 expression abrogates and reverses norepinephrine-induced myocyte hypertrophy by CaMKII inhibition. Journal of molecular and cellular cardiology 13 30462989
2015 Two novel Brugada syndrome-associated mutations increase KV4.3 membrane expression and function. International journal of molecular medicine 13 26016905
2015 Kv4.3-Encoded Fast Transient Outward Current Is Presented in Kv4.2 Knockout Mouse Cardiomyocytes. PloS one 13 26196737
2012 Duloxetine blocks cloned Kv4.3 potassium channels. Brain research 13 22618310
2011 Central role of PKCα in isoenzyme-selective regulation of cardiac transient outward current Ito and Kv4.3 channels. Journal of molecular and cellular cardiology 13 21803046
2009 Divergent regulation of cardiac KCND3 potassium channel expression by the thyroid hormone receptors alpha1 and beta1. The Journal of physiology 13 19171649
2009 Closed-state inactivation in Kv4.3 isoforms is differentially modulated by protein kinase C. American journal of physiology. Cell physiology 13 19675305

Missed literature

Know a paper Affinage missed for KCND3? Flag it for the maintainers and the community.

No submissions yet.