Affinage

KCNK1

Potassium channel subfamily K member 1 · UniProt O00180

Length
336 aa
Mass
38.1 kDa
Annotated
2026-06-10
37 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNK1 (TWIK-1) is a two-pore-domain, four-transmembrane-segment background K+ channel with a novel architecture that produces time-independent, weakly inward-rectifying currents modulated by PKC and intracellular acidification (PMID:8605869). Functional channels assemble as disulfide-linked homodimers through Cys69 in the extracellular M1P1 linker, and this bond is required for channel expression and is detectable as a reducing-agent-sensitive ~81 kDa species in native brain (PMID:8978667, PMID:9013852). The same C69 chemistry allows TWIK-1 to form covalent heterodimers with TREK-1 (C69–C93) and to associate with TASK-3, generating channels with distinct rectification and physiological roles (PMID:24496152, PMID:30416196). A defining feature of TWIK-1 is its low intrinsic activity, which arises from instability of the selectivity-filter gate rather than from intracellular retention or a hydrophobic pore barrier; K+ poorly stabilizes the conductive conformation, whereas Rb+, NH4+, and Cs+ promote a pH-dependent active state (PMID:31806709). Under hypokalemia the channel changes selectivity and conducts inward Na+ leak currents through a Thr118-dependent mechanism, driving paradoxical depolarization in cardiomyocytes (PMID:21653227). TWIK-1 is predominantly intracellular but is recruited to the plasma membrane by Gi/Go-coupled mGluR3 signaling via Rab-dependent recycling endosome trafficking (PMID:24368895, PMID:26553349). At the astrocyte surface it mediates background passive K+ conductance, and a true null mouse establishes that loss of TWIK-1 abolishes this conductance and increases susceptibility to kainic-acid-induced seizures (PMID:39811670); it also shapes resting potential and intrinsic excitability of dentate granule cells (PMID:25406588). Beyond ion conduction, KCNK1 non-canonically binds and activates LDHA to drive glycolytic reprogramming and histone lactylation in breast cancer (PMID:38905316), and modulates Ca2+/JNK signaling to inhibit osteoclastogenesis (PMID:26208638). Its expression is controlled transcriptionally by the nuclear receptor CAR (PMID:23291559) and post-transcriptionally by the RNA-binding protein AEG-1, which stabilizes TWIK-1 mRNA (PMID:33440655).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1996 High

    Established that KCNK1 defines a new K+ channel class, answering what kind of conductance it produces and how it is gated.

    Evidence Heterologous expression in Xenopus oocytes with two-electrode voltage clamp, single-channel recording, and pharmacology

    PMID:8605869

    Open questions at the time
    • No structural basis for inward rectification defined
    • Native cellular role not yet addressed
  2. 1996 High

    Defined the assembly mechanism by showing functional channels require a covalent dimer, answering how subunits oligomerize.

    Evidence Biochemical dimerization assay and C69S site-directed mutagenesis with functional expression

    PMID:8978667 PMID:9013852

    Open questions at the time
    • Whether C69 also mediates heterodimerization not yet tested
    • Stoichiometry beyond dimer not addressed
  3. 2011 High

    Resolved how a 'silent' K+ channel can depolarize cells by demonstrating hypokalemia-induced Na+ permeability through Thr118.

    Evidence Patch clamp with T118 mutagenesis plus shRNA knockdown in primary human cardiomyocytes

    PMID:21653227

    Open questions at the time
    • Physiological contexts where this leak operates beyond cardiomyocytes unclear
    • Structural mechanism of selectivity switch not solved
  4. 2012 Medium

    Clarified the source of channel silencing by showing it reflects gating behavior rather than absent surface expression.

    Evidence Patch clamp of TWIK-1 in CHO cells under varied extracellular ionic conditions

    PMID:22768960

    Open questions at the time
    • Single method, single cell line
    • Molecular identity of the gate not yet defined
  5. 2013 Medium

    Identified transcriptional and subcellular determinants of KCNK1 abundance and a hepatic phenotype, addressing how the gene is regulated and what it does outside neurons.

    Evidence ChIP mapping CAR binding to the Kcnk1 promoter and Kcnk1-/- mouse liver hyperplasia analysis; subcellular fractionation in astrocytes

    PMID:23291559 PMID:24368895

    Open questions at the time
    • Mechanism linking K+ conductance to hyperplasia suppression unknown
    • Retention/trafficking machinery not identified in these studies
  6. 2014 High

    Showed KCNK1 functions through heterodimerization, establishing a TWIK-1/TREK-1 channel that carries astrocytic passive conductance.

    Evidence Reciprocal Co-IP, C69/C93 disulfide mutagenesis, shRNA silencing, and astrocyte electrophysiology with glutamate release assay

    PMID:24496152

    Open questions at the time
    • Relative contribution versus homodimers in vivo unresolved
    • Later genetic studies contested the conductance claim
  7. 2014 Medium

    Extended the channel's role to neuronal excitability by defining its impact on granule cell membrane properties.

    Evidence Immunolocalization, shRNA silencing, and patch clamp in hippocampal slices

    PMID:25406588

    Open questions at the time
    • Homodimer versus heterodimer identity not resolved here
    • Knockdown rather than genetic null
  8. 2015 Medium

    Identified a second heterodimer partner and a receptor pathway controlling it, showing TWIK-1/TASK-3 sets granule cell excitability under neurotensin signaling.

    Evidence Co-IP, immunohistochemistry, shRNA silencing, and pharmacological NT-NTSR1 activation with patch clamp

    PMID:30416196

    Open questions at the time
    • Direct disulfide linkage with TASK-3 not demonstrated
    • Single lab
  9. 2015 Medium

    Revealed non-conduction functions of KCNK1 in bone, addressing whether the channel signals beyond K+ flux.

    Evidence Gain- and loss-of-function in osteoclast precursors with Ca2+ imaging, JNK, and NFATc1 readouts

    PMID:26208638

    Open questions at the time
    • Whether ion conduction is required for osteoclast effect unclear
    • In vivo bone phenotype not tested
  10. 2015 Low

    Probed the structural basis of pore dewetting through simulation of lipid and side-chain contributions to hydration.

    Evidence Molecular dynamics simulations on the TWIK-1 crystal structure

    PMID:25487004

    Open questions at the time
    • Computational only, no experimental validation
    • Functional consequence of dewetting not tested in cells
  11. 2015 Medium

    Defined how the intracellular pool reaches the surface, showing mGluR3-driven Rab-dependent trafficking recruits TWIK-1 to the membrane.

    Evidence Live-cell imaging of translocation, patch clamp, pharmacological mGluR3 activation, KO controls, and Rab-pathway inhibition

    PMID:26553349

    Open questions at the time
    • Specific Rab isoform and adaptors not pinned down
    • Whether trafficking applies to heterodimers unknown
  12. 2016 Medium

    Provided an in vivo organismal phenotype and rescue, addressing the physiological consequence of KCNK1 loss in the heart.

    Evidence Zebrafish morpholino knockdown with WT and dominant-negative human KCNK1 mRNA rescue, oocyte electrophysiology, and localization

    PMID:27103460

    Open questions at the time
    • Morpholino off-target effects not fully excluded
    • Mammalian cardiac requirement not established
  13. 2016 Medium

    Challenged the heterodimer-conductance model by showing genetic deletion of TREK-1 and TWIK-1/TREK-1 leaves astrocyte passive conductance intact.

    Evidence TREK-1 single and TWIK-1/TREK-1 double KO mice with in situ astrocyte patch clamp, immunofluorescence, and qRT-PCR

    PMID:26869883

    Open questions at the time
    • Discrepancy with knockdown studies unresolved at the time
    • Possible compensatory channels not excluded
  14. 2019 High

    Resolved the mechanism of intrinsic silencing, establishing that selectivity-filter gate instability—not retention or a hydrophobic barrier—limits activity.

    Evidence Two-electrode voltage clamp with systematic ion substitution and intracellular K+ variation, testing competing gating hypotheses

    PMID:31806709

    Open questions at the time
    • Physiological permeant ion that activates the SF in vivo unclear
    • Link between SF gating and Na+ leak under hypokalemia not unified
  15. 2020 Medium

    Reinforced the heterodimer conductance model pharmacologically, showing spadin-sensitive currents are mediated by TWIK-1/TREK-1.

    Evidence Spadin inhibition combined with shRNA silencing and patch clamp in slices and cultured astrocytes

    PMID:33348878

    Open questions at the time
    • Reconciliation with the negative double-KO result not provided
    • Spadin specificity for the heterodimer not independently validated
  16. 2021 Medium

    Identified post-transcriptional control of KCNK1, showing AEG-1 stabilizes TWIK-1 mRNA to sustain channel function.

    Evidence RNA immunoprecipitation, shRNA knockdown, qPCR, and patch clamp in astrocytes

    PMID:33440655

    Open questions at the time
    • Binding site on TWIK-1 mRNA not mapped
    • Physiological trigger for AEG-1 regulation unknown
  17. 2024 Medium

    Uncovered a moonlighting metabolic function, showing KCNK1 binds and activates LDHA to drive glycolysis and histone lactylation in cancer.

    Evidence Co-IP, glycolysis/lactate and histone lactylation assays, knockdown/overexpression, and in vitro/in vivo tumor models

    PMID:38905316

    Open questions at the time
    • Whether channel activity contributes to LDHA binding unknown
    • Structural basis of the KCNK1-LDHA interaction undefined
  18. 2024 Medium

    Extended KCNK1's role to vascular smooth muscle, linking the channel to proliferation via Ca2+ and JNK signaling.

    Evidence siRNA knockdown in patient-derived IPAH PASMCs with membrane potential, Ca2+ imaging, and JNK readouts

    PMID:38410243

    Open questions at the time
    • Single patient-derived cell system
    • Causal disease role in IPAH not established in vivo
  19. 2024 High

    Provided a definitive genetic test using a true null mouse, establishing that TWIK-1 mediates astrocytic passive conductance and protects against seizures, and correcting flawed prior KO models.

    Evidence CRISPR-Cas9 exon 1 knockout mouse with astrocyte patch clamp and kainic acid seizure assay, compared to exon 2-deleted mice

    PMID:39811670

    Open questions at the time
    • Homodimer versus heterodimer basis of the conductance not dissected here
    • Reconciliation with prior negative TREK-1 double-KO not fully addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the selectivity-filter gating, the hypokalemia Na+ leak, the trafficking control, and the non-canonical LDHA-binding function are integrated into a single physiological logic remains unresolved.
  • No unified structural model linking gate instability to Na+ leak
  • Whether moonlighting LDHA/osteoclast roles require channel conduction is untested
  • Mendelian disease association via direct genetic evidence absent from the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-112316 Neuronal System 3
Partners
KCNK2KCNK9LDHAMTDHNR1I3
Complex memberships
TWIK-1 homodimerTWIK-1/TASK-3 heterodimerTWIK-1/TREK-1 heterodimer

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 TWIK-1 (KCNK1) is a K+ channel with four transmembrane domains and two pore-forming P domains (novel architecture). Expressed in Xenopus oocytes, it produces time-independent, weakly inward-rectifying currents with a unitary conductance of 34 pS. Inward rectification requires internal Mg2+. Channel activity is up-regulated by protein kinase C activation and down-regulated by internal acidification. Blocked by Ba2+ (IC50=100 µM), quinine (IC50=50 µM), and quinidine (IC50=95 µM). Heterologous expression in Xenopus oocytes, two-electrode voltage clamp, single-channel recording, pharmacology The EMBO journal High 8605869
1996 TWIK-1 subunits dimerize via an interchain disulfide bridge. A 34-amino-acid domain in the extracellular M1P1 linker loop mediates self-association. Cysteine 69 forms the disulfide bond; replacing C69 with serine abolishes functional K+ channel expression. Biochemical dimerization assay, site-directed mutagenesis (C69S), functional expression in Xenopus oocytes The EMBO journal High 8978667
1997 Native mouse TWIK-1 (mTWIK-1) protein in brain runs at ~81 kDa; treatment with a reducing agent yields a ~40 kDa form, confirming that native subunits dimerize via a disulfide bridge in vivo. In oocytes, mTWIK-1 currents are K+-selective, instantaneous, and weakly inward-rectifying; they are blocked by Ba2+ and quinine, decreased by PKC activation, and increased by internal acidification. Western blot with/without reducing agent, Xenopus oocyte expression, two-electrode voltage clamp FEBS letters High 9013852
2011 In subphysiological extracellular K+ (hypokalemia), human TWIK-1 channels change ion selectivity, becoming permeable to external Na+, and conduct inward leak Na+ currents. Threonine 118 (Thr118) within the pore selectivity sequence TxGYG is required for this altered selectivity. Knockdown of TWIK-1 in human spherical primary cardiac myocytes eliminated paradoxical depolarization in low [K+]o. Heterologous expression, patch clamp, site-directed mutagenesis (T118), shRNA knockdown in cardiomyocytes, ectopic expression in HL-1 cells Science signaling High 21653227
2014 Native TWIK-1 forms a functional heterodimeric channel with TREK-1 at the plasma membrane of astrocytes, linked by a disulfide bridge between TWIK-1 C69 and TREK-1 C93. Surface expression of TWIK-1 and TREK-1 are interdependent (gene silencing of one reduces surface expression of the other). The TWIK-1/TREK-1 heterodimer mediates astrocytic passive conductance and cannabinoid-induced glutamate release from astrocytes. Co-immunoprecipitation, pulldown for binding partner identification, site-directed mutagenesis (C69, C93), shRNA gene silencing, electrophysiology in astrocytes, glutamate release assay Nature communications High 24496152
2013 TWIK-1 protein is primarily localized in intracellular cytoplasmic fractions (~55%) and mildly hydrophobic internal compartment fractions (~41%) in hippocampal astrocytes, with only ~5% at the plasma membrane. This predominant intracellular retention accounts for the minimal contribution of TWIK-1 to whole-cell passive conductance despite abundant expression. Subcellular fractionation, TWIK-1 knockout mouse comparison, whole-cell patch clamp in astrocytes Frontiers in cellular neuroscience Medium 24368895
2014 TWIK-1 is expressed in the soma and proximal dendrites of dentate gyrus granule cells (DGGCs). Gene silencing of TWIK-1 reduces outwardly rectifying K+ current density, causes depolarizing shift in resting membrane potential, enhances firing rate, increases EPSP amplitude, and impairs EPSP-spike coupling in perforant path-to-granule cell synaptic transmission. Immunolocalization, shRNA gene silencing, whole-cell patch clamp, perforant path stimulation in hippocampal slices Molecular brain Medium 25406588
2015 TWIK-1 forms a heterodimeric channel with TASK-3 in dentate gyrus granule cells (DGGCs). The TWIK-1/TASK-3 heterodimer displays outwardly rectifying currents and contributes to intrinsic excitability of DGGCs. Neurotensin-neurotensin receptor 1 (NT-NTSR1) signaling depolarizes DGGCs by inhibiting TWIK-1/TASK-3 heterodimeric channels. Co-immunoprecipitation, immunohistochemistry, shRNA gene silencing, whole-cell patch clamp, pharmacological NT-NTSR1 activation in hippocampal slices Experimental & molecular medicine Medium 30416196
2019 The low intrinsic activity of TWIK-1 is dominated by instability of the selectivity filter (SF) gate in a conductive conformation, rather than by sumoylation, intracellular retention, or a hydrophobic pore barrier. K+ is inefficient at stabilizing an active SF conformation; Rb+, NH4+, and Cs+ promote a pH-dependent activated conformation. Intracellular K+ potently inhibits TWIK-1 Rb+ currents (IC50 = 2.8 mM). Voltage-dependent activation of TWIK-1 via an SF mechanism requires non-physiological strong depolarization. Heterologous expression, two-electrode voltage clamp in Xenopus oocytes, ion substitution experiments, patch clamp with varied intracellular K+, systematic evaluation of competing gating mechanisms The Journal of biological chemistry High 31806709
2015 Lipid tails from both membrane leaflets can enter fenestrations in the TWIK-1 structure and partially penetrate into the pore, contributing to dewetting. However, dewetting still occurs in the absence of lipid tails; pore hydration is determined primarily by hydrophobic side chains lining the narrowest pore cavity. Molecular dynamics (MD) simulations using TWIK-1 crystal structure Channels (Austin, Tex.) Low 25487004
2015 mGluR3 activation (Gi/Go-coupled) induces translocation of TWIK-1 channels from intracellular cytoplasm to the plasma membrane surface via a Rab-mediated recycling endosome trafficking pathway. This membrane recruitment enhances NH4+ uptake in hippocampal astrocytes and causes membrane potential depolarization. Live-cell imaging of TWIK-1 translocation, whole-cell patch clamp, pharmacological mGluR3 activation, TWIK-1 KO astrocytes as controls, Rab-pathway inhibition Molecular neurobiology Medium 26553349
2012 TWIK-1 channels heterologously expressed in CHO cells, which are silent in physiological K+ gradients, can conduct large monovalent cation currents when extracellular ionic conditions change, supporting the hypothesis that channel silencing results from gating behavior rather than lack of cell surface expression. Heterologous expression in CHO cells, patch clamp with varied extracellular ionic conditions Biophysical journal Medium 22768960
2013 Nuclear receptor CAR (constitutive androstane receptor) directly binds a 97-bp response element (−2441/−2345) in the Kcnk1 promoter in male mouse livers upon phenobarbital treatment. This binding is male-specific and requires the pituitary gland. KCNK1 suppresses phenobarbital-induced hepatic hyperplasia, as Kcnk1−/− male mice show further progression of liver hyperplasia. ChIP assay, Kcnk1 knockout mouse model, promoter-response element mapping, hypophysectomy experiment Toxicological sciences Medium 23291559
2016 Zebrafish knockdown of kcnk1a or kcnk1b orthologues causes bradycardia and atrial dilation; combined knockdown produces a more severe phenotype that is partially rescued by co-injection of wild-type human KCNK1 mRNA but not by a dominant-negative KCNK1 variant. Both zebrafish and human TWIK-1 channels predominantly localize to the endosomal compartment in transfected cells and produce K+ currents sensitive to external K+ concentration and acidic pH. Zebrafish morpholino knockdown, mRNA rescue experiments (WT and dominant-negative), two-electrode voltage clamp in Xenopus oocytes, cellular localization in transfected mammalian cells Journal of molecular and cellular cardiology Medium 27103460
2016 TREK-1 single and TWIK-1/TREK-1 double gene knockout in mice produced no detectable changes in astrocyte passive conductance, resting membrane potential, or membrane input resistance in hippocampal astrocytes in situ. TREK-1 protein was mainly located in intracellular compartments of hippocampus. This negative result challenges the proposed essential contribution of TWIK-1/TREK-1 heterodimers to astrocyte passive conductance. TREK-1 single KO and TWIK-1/TREK-1 double KO mouse models, whole-cell patch clamp of hippocampal astrocytes in situ, immunofluorescence, qRT-PCR Frontiers in cellular neuroscience Medium 26869883
2015 KCNK1 inhibits osteoclast differentiation induced by RANKL. Overexpression of KCNK1 attenuates RANKL-induced Ca2+ oscillation, JNK activation, and NFATc1 expression; conversely, KCNK1 knockdown enhances osteoclast differentiation, JNK activation, and NFATc1 expression. Overexpression and shRNA knockdown in osteoclast precursors, Ca2+ imaging, JNK phosphorylation assay, NFATc1 expression assay, osteoclast differentiation assay Journal of cell science Medium 26208638
2024 KCNK1 binds to and activates lactate dehydrogenase A (LDHA) in breast cancer cells, increasing glycolysis and lactate production. This promotes histone lysine lactylation (H3K18 lactylation), which induces downstream gene expression including LDHA itself (positive feedback). Increased LDHA also reduces tumor cell stiffness and adhesion. Co-immunoprecipitation (KCNK1-LDHA binding), glycolysis/lactate production assays, histone lactylation measurement, siRNA knockdown and overexpression, in vitro and in vivo tumor models PLoS biology Medium 38905316
2021 AEG-1 (MTDH) directly binds TWIK-1 mRNA as an RNA-binding protein in astrocytes, stabilizing it. AEG-1 knockdown reduces TWIK-1 mRNA and protein levels and decreases TWIK-1-mediated K+ currents; AEG-1 overexpression increases TWIK-1 mRNA stability. RNA immunoprecipitation (RIP), shRNA knockdown, qPCR, immunocytochemistry, whole-cell patch clamp electrophysiology in astrocytes Brain sciences Medium 33440655
2020 Spadin, an inhibitor of TREK-1, dramatically reduces astrocytic passive conductance in brain slices. Gene silencing experiments demonstrated that spadin-sensitive currents are mediated specifically by TWIK-1/TREK-1 heterodimeric channels in cultured astrocytes and hippocampal astrocytes from brain slices. Pharmacological inhibition with spadin, shRNA gene silencing of TWIK-1 and TREK-1, whole-cell patch clamp in brain slices and cultured astrocytes International journal of molecular sciences Medium 33348878
2024 KCNK1 siRNA knockdown in IPAH pulmonary arterial smooth muscle cells (PASMCs) suppresses their proliferation and migration, causes membrane depolarization, decreases cytosolic Ca2+, and reduces JNK phosphorylation. Up-regulated KCNK1 in IPAH-PASMCs thus facilitates proliferation/migration via membrane hyperpolarization-dependent Ca2+ signaling and JNK pathway activation. siRNA knockdown, cell proliferation and migration assays, membrane potential measurement, cytosolic Ca2+ imaging, JNK phosphorylation assay in patient-derived PASMCs Frontiers in cardiovascular medicine Medium 38410243
2024 TWIK-1-null mice (exon 1 CRISPR-Cas9 KO) exhibit loss of astrocytic background passive K+ conductance and increased susceptibility to kainic acid-induced seizures, establishing that TWIK-1 mediates astrocytic passive conductance and that its loss promotes neuronal hyperexcitability. The previously used exon 2-deleted mice unexpectedly produce a functional internally deleted TWIK-1 protein. CRISPR-Cas9 exon 1 knockout mouse, whole-cell patch clamp of astrocytes, kainic acid seizure susceptibility assay, comparison with exon 2-deleted KO mice iScience High 39811670

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. The EMBO journal 434 8605869
2009 TWIK-1 and TREK-1 are potassium channels contributing significantly to astrocyte passive conductance in rat hippocampal slices. The Journal of neuroscience : the official journal of the Society for Neuroscience 145 19571146
1996 Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge. The EMBO journal 145 8978667
2014 A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. Nature communications 121 24496152
1997 The structure, function and distribution of the mouse TWIK-1 K+ channel. FEBS letters 100 9013852
2024 KCNK1 promotes proliferation and metastasis of breast cancer cells by activating lactate dehydrogenase A (LDHA) and up-regulating H3K18 lactylation. PLoS biology 76 38905316
2011 TWIK-1 two-pore domain potassium channels change ion selectivity and conduct inward leak sodium currents in hypokalemia. Science signaling 66 21653227
2018 TWIK-1/TASK-3 heterodimeric channels contribute to the neurotensin-mediated excitation of hippocampal dentate gyrus granule cells. Experimental & molecular medicine 65 30416196
2005 Expression and insights on function of potassium channel TWIK-1 in mouse kidney. Pflugers Archiv : European journal of physiology 43 16025300
2016 Genetic Deletion of TREK-1 or TWIK-1/TREK-1 Potassium Channels does not Alter the Basic Electrophysiological Properties of Mature Hippocampal Astrocytes In Situ. Frontiers in cellular neuroscience 37 26869883
1998 Expression of TWIK-1, a novel weakly inward rectifying potassium channel in rat kidney. The American journal of physiology 36 9843722
2013 The contribution of TWIK-1 channels to astrocyte K(+) current is limited by retention in intracellular compartments. Frontiers in cellular neuroscience 33 24368895
1997 Cloning and localization of a double-pore K channel, KCNK1: exclusive expression in distal nephron segments. The American journal of physiology 31 9362344
2016 The two-pore domain potassium channel, TWIK-1, has a role in the regulation of heart rate and atrial size. Journal of molecular and cellular cardiology 30 27103460
2019 Selectivity filter instability dominates the low intrinsic activity of the TWIK-1 K2P K+ channel. The Journal of biological chemistry 23 31806709
2015 Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel. Channels (Austin, Tex.) 23 25487004
2014 TWIK-1 contributes to the intrinsic excitability of dentate granule cells in mouse hippocampus. Molecular brain 22 25406588
2003 Cellular localization of TWIK-1, a two-pore-domain potassium channel in the rodent inner ear. Hearing research 20 12855359
2006 Adaptive downregulation of a quinidine-sensitive cation conductance in renal principal cells of TWIK-1 knockout mice. Pflugers Archiv : European journal of physiology 17 16847696
2012 Silent TWIK-1 potassium channels conduct monovalent cation currents. Biophysical journal 16 22768960
2015 KCNK1 inhibits osteoclastogenesis by blocking the Ca2+ oscillation and JNK-NFATc1 signaling axis. Journal of cell science 14 26208638
2013 Nuclear receptor CAR specifically activates the two-pore K+ channel Kcnk1 gene in male mouse livers, which attenuates phenobarbital-induced hepatic hyperplasia. Toxicological sciences : an official journal of the Society of Toxicology 14 23291559
2015 mGluR3 Activation Recruits Cytoplasmic TWIK-1 Channels to Membrane that Enhances Ammonium Uptake in Hippocampal Astrocytes. Molecular neurobiology 12 26553349
2024 Up-regulated expression of two-pore domain K+ channels, KCNK1 and KCNK2, is involved in the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary arterial hypertension. Frontiers in cardiovascular medicine 11 38410243
2016 Exploring the Dynamics of the TWIK-1 Channel. Biophysical journal 11 27558721
2020 Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels. International journal of molecular sciences 10 33348878
2023 Downregulation of ciRNA-Kat6b in dorsal spinal horn is required for neuropathic pain by regulating Kcnk1 in miRNA-26a-dependent manner. CNS neuroscience & therapeutics 9 37144575
2017 Emerging Roles of TWIK-1 Heterodimerization in the Brain. International journal of molecular sciences 9 29295556
2024 Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer. European journal of medical research 6 38689322
2023 The Effect of TWIK-1 Two Pore Potassium Channels on Cardiomyocytes in Low Extracellular Potassium Conditions. Frontiers in bioscience (Landmark edition) 4 37005754
2021 TWIK-1 BAC-GFP Transgenic Mice, an Animal Model for TWIK-1 Expression. Cells 4 34685731
2025 Genetic Variants in SDC3, KCNA2, KCNK1, KCNK16, and Heat Shock Transcription Factor-1 Genes: An Exploratory Analysis Supporting the Piezo2 Channelopathy Hypothesis in Amyotrophic Lateral Sclerosis Onset. International journal of molecular sciences 1 41155507
2024 Evidence for an Association Between a pH-Dependent Potassium Channel, TWIK-1, and the Accuracy of Smooth Pursuit Eye Movements. Investigative ophthalmology & visual science 1 39012638
2021 AEG-1 Regulates TWIK-1 Expression as an RNA-Binding Protein in Astrocytes. Brain sciences 1 33440655
2025 The preference for ammonium may be attributed to a hyperpolarized membrane potential via TWIK-1 channels. Brain research 0 41386584
2024 Exploring the Role of the KCNK1 Potassium Channel and Its Inhibition Using Quinidine in Treating Head and Neck Squamous Cell Carcinoma. Clinical and experimental otorhinolaryngology 0 39639713
2024 Mice deficient in TWIK-1 are more susceptible to kainic acid-induced seizures. iScience 0 39811670

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