Affinage

KCNK1

Potassium channel subfamily K member 1 · UniProt O00180

Length
336 aa
Mass
38.1 kDa
Annotated
2026-04-28
42 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNK1 (TWIK-1) is a two-pore-domain potassium channel that assembles as a disulfide-linked homodimer (via Cys69) or as heterodimers with TREK-1 (via Cys69–Cys93) or TASK-3, and sets resting membrane potential in hippocampal astrocytes and dentate granule neurons (PMID:8978667, PMID:24496152, PMID:30416196, PMID:25406588). The channel is constitutively retained in intracellular compartments with only ~5% at the plasma membrane, and surface delivery is stimulated by mGluR3/Gi–Rab-dependent trafficking from recycling endosomes (PMID:24368895, PMID:26553349). Its selectivity filter, which contains the non-canonical residue Thr118, is intrinsically unstable in physiological K+, accounting for low basal activity, but switches to Na+ permeability under hypokalemic conditions, contributing to paradoxical depolarization in cardiac myocytes (PMID:31806709, PMID:21653227). Astrocytic TWIK-1-mediated passive conductance is neuroprotective, as TWIK-1 knockout mice show increased seizure susceptibility to kainic acid (PMID:39811670).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    Establishing KCNK1 as the founding two-pore-domain K+ channel resolved its basic biophysical identity: a time-independent, weakly inward-rectifying K+ conductance modulated by PKC and intracellular pH, with a defined pharmacological profile (Ba2+, quinine blockade).

    Evidence Heterologous expression and patch-clamp in Xenopus oocytes

    PMID:8605869

    Open questions at the time
    • Physiological context unknown
    • Mechanism of PKC up-regulation not delineated
    • Gating mechanism at molecular level unresolved
  2. 1996 High

    Demonstrating that TWIK-1 assembles as a disulfide-linked homodimer via Cys69 established the structural basis for channel formation and showed that dimerization is required for function.

    Evidence Site-directed mutagenesis (C69S) and biochemical dimerization assay in oocytes, confirmed by Western blot of native mouse brain protein

    PMID:8978667 PMID:9013852

    Open questions at the time
    • Whether heterodimers form in vivo unknown
    • Structure beyond dimerization interface unresolved
  3. 2009 High

    Identifying TWIK-1 as a major contributor to background passive conductance in hippocampal astrocytes placed the channel in a defined physiological context and explained its role in setting astrocytic resting membrane potential.

    Evidence Patch-clamp in CHO cells and hippocampal slices with quinine pharmacology and immunocytochemistry

    PMID:19571146

    Open questions at the time
    • Relative contribution versus other K2P channels not fully dissected
    • Mechanism of intracellular retention unclear
  4. 2011 High

    Discovering that TWIK-1 switches from K+- to Na+-permeable under hypokalemia, dependent on selectivity filter residue Thr118, revealed a dynamic ion selectivity mechanism with direct pathophysiological relevance for cardiac depolarization.

    Evidence Site-directed mutagenesis of T118, siRNA knockdown in human primary cardiac myocytes, patch-clamp

    PMID:21653227

    Open questions at the time
    • Structural basis of selectivity switch not experimentally determined
    • In vivo cardiac phenotype in mammals not established
  5. 2013 High

    Subcellular fractionation and knockout studies showed that ~95% of TWIK-1 is retained intracellularly, explaining its low functional surface activity and reconciling the discrepancy between high transcript abundance and modest whole-cell current.

    Evidence Subcellular fractionation of astrocytes, TWIK-1 knockout mice with electrophysiology

    PMID:24368895

    Open questions at the time
    • Molecular machinery mediating intracellular retention not identified
    • Whether retention is constitutive or dynamically regulated was unclear
  6. 2014 High

    Identification of TWIK-1/TREK-1 heterodimers linked by a Cys69–Cys93 disulfide bridge established that TWIK-1 forms obligate heteromeric channels at the astrocyte surface, mediating passive conductance and cannabinoid-induced glutamate release, and later confirmed as spadin-sensitive channels.

    Evidence Reciprocal Co-IP, mutagenesis, surface biotinylation, gene silencing, patch-clamp in astrocytes; pharmacology with spadin

    PMID:24496152 PMID:33348878

    Open questions at the time
    • Stoichiometry and structure of heterodimer not resolved
    • Whether TWIK-1 homodimers also contribute at the surface remains debated
  7. 2014 High

    Gene silencing in dentate granule cells revealed that TWIK-1 carries outwardly rectifying currents that maintain hyperpolarized resting potential and modulate synaptic integration at the perforant path, establishing a neuronal (not only glial) role.

    Evidence shRNA in mouse hippocampal DGGCs with patch-clamp electrophysiology

    PMID:25406588

    Open questions at the time
    • Whether the neuronal current is homodimeric or heterodimeric unresolved at this point
  8. 2015 Medium

    Demonstrating that mGluR3 activation drives Rab-dependent translocation of TWIK-1 from cytoplasm to plasma membrane identified a receptor-mediated trafficking mechanism that dynamically regulates astrocytic TWIK-1 surface expression.

    Evidence Live-cell imaging, electrophysiology, pharmacological mGluR3 activation, TWIK-1 KO comparison in astrocytes

    PMID:26553349

    Open questions at the time
    • Specific Rab isoform not identified
    • Signaling intermediates between Gi/Go and Rab machinery not mapped
    • Single-lab finding
  9. 2016 High

    Zebrafish knockdown of kcnk1a/b causing bradycardia and atrial dilation, rescuable by human KCNK1, established a conserved cardiac pacemaking role and confirmed predominant endosomal localization across species.

    Evidence Morpholino knockdown in zebrafish with human mRNA rescue, electrophysiology in oocytes

    PMID:27103460

    Open questions at the time
    • Mammalian in vivo cardiac phenotype not confirmed
    • Channel composition in cardiomyocytes (homo- vs heterodimer) unknown
  10. 2018 High

    Identification of TWIK-1/TASK-3 heterodimers in dentate granule cells, inhibited by neurotensin-NTSR1 signaling, resolved the composition of the neuronal TWIK-1 channel and linked it to a neuromodulatory pathway.

    Evidence Reciprocal Co-IP in hippocampal tissue and COS-7 cells, shRNA, patch-clamp, NTSR1 pharmacology

    PMID:30416196

    Open questions at the time
    • Proportion of TWIK-1 in homodimer vs TASK-3 heterodimer in neurons not quantified
    • Downstream behavioral consequences of NTSR1-mediated inhibition unexplored
  11. 2019 High

    Systematic electrophysiological dissection showed that the primary mechanism underlying TWIK-1's low basal activity is instability of the selectivity filter conductive state in K+, rather than previously proposed sumoylation or internalization, resolving a long-standing debate.

    Evidence Patch-clamp with multiple permeant ions (Rb+, NH4+, Cs+), mutagenesis, pharmacology

    PMID:31806709

    Open questions at the time
    • Structural dynamics of SF gating not captured experimentally
    • Whether SF instability is modulated by heterodimer partners unknown
  12. 2024 High

    CRISPR-Cas9 full knockout of TWIK-1 demonstrated that astrocytic TWIK-1 passive conductance is neuroprotective, as KO mice show heightened seizure susceptibility to kainic acid, resolving a prior artifact from partial exon-2 deletion.

    Evidence Exon 1 CRISPR-Cas9 KO mice, patch-clamp in astrocytes, kainic acid seizure model

    PMID:39811670

    Open questions at the time
    • Whether seizure phenotype is astrocyte-autonomous vs includes neuronal TWIK-1 loss not distinguished
    • Rescue experiment not performed
  13. 2024 Medium

    An unexpected non-channel function was reported: KCNK1 directly binds and activates LDHA, promoting glycolysis, histone H3K18 lactylation, and a positive-feedback transcriptional loop that drives breast cancer proliferation and metastasis.

    Evidence Co-IP of KCNK1-LDHA, glycolysis/lactate assays, histone lactylation analysis, xenograft models

    PMID:38905316

    Open questions at the time
    • Whether this function requires channel activity is untested
    • No independent replication
    • Structural basis of KCNK1-LDHA interaction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of selectivity filter gating and the Na+-permeability switch, how heterodimer partner choice (TREK-1 vs TASK-3) is determined in different cell types, the molecular machinery mediating constitutive intracellular retention, and whether the non-channel LDHA-activating function is physiologically relevant beyond cancer.
  • No high-resolution structure of full-length TWIK-1 in active/inactive states
  • In vivo mammalian cardiac phenotype not established
  • Channel-independent functions lack independent replication

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 8 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 3 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3
Partners
KCNK2KCNK9LDHAMTDH
Complex memberships
TWIK-1 homodimerTWIK-1/TASK-3 heterodimerTWIK-1/TREK-1 heterodimer

Evidence

Reading pass · 22 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; it produces time-independent, weakly inward-rectifying currents in Xenopus oocytes; inward rectification requires internal Mg2+; the channel has a unitary conductance of 34 pS; activity is up-regulated by PKC activation and down-regulated by internal acidification; it is blocked by Ba2+, quinine, and quinidine. Heterologous expression in Xenopus oocytes, patch-clamp electrophysiology, pharmacology The EMBO journal High 8605869
1996 TWIK-1 subunits self-associate into homodimers via an interchain disulfide bridge involving Cys69 in the extracellular M1P1 linker loop; mutation of C69 to serine abolishes functional K+ channel expression. Biochemical dimerization assay, site-directed mutagenesis (C69S), functional expression in Xenopus oocytes The EMBO journal High 8978667
1997 Mouse TWIK-1 (mTWIK-1) has an apparent native molecular weight of ~81 kDa; treatment with reducing agent reveals a ~40 kDa form, confirming native dimerization via a disulfide bridge; mTWIK-1 currents in oocytes are K+-selective, instantaneous, and weakly inward-rectifying; blocked by Ba2+ and quinine; decreased by PKC and increased by internal acidification. Western blot with/without reducing agent, heterologous expression in Xenopus oocytes, electrophysiology FEBS letters High 9013852
2009 TWIK-1 contributes to the background passive K+ conductance of mature hippocampal astrocytes; cloned rat TWIK-1 in CHO cells conducts Cs+ currents (PCs/PK = 0.10); astrocytic passive conductance is inhibited ~58% by 200 µM quinine (IC50 for TWIK-1 = 85 µM); TWIK-1 protein co-localizes with astrocytic markers GLAST and GFAP in hippocampal stratum radiatum. Patch-clamp electrophysiology in CHO cells and hippocampal slices, pharmacology, immunocytochemistry The Journal of neuroscience High 19571146
2011 TWIK-1 changes ion selectivity from K+-selective to Na+-permeable under subphysiological extracellular K+ (hypokalemia), conducting inward leak Na+ currents; Thr118 within the selectivity filter sequence TxGYG is required for this altered selectivity; TWIK-1 knockdown in human primary cardiac myocytes eliminates paradoxical depolarization in low [K+]o. Patch-clamp electrophysiology, site-directed mutagenesis (T118 variants), siRNA knockdown in human spherical primary cardiac myocytes, ectopic expression in HL-1 and CHO cells Science signaling High 21653227
2013 TWIK-1 is primarily localized in intracellular cytoplasmic compartments (~55%) and mildly hydrophobic internal compartment fractions (~41%), with only ~5% at the plasma membrane of hippocampal astrocytes, limiting its contribution to whole-cell passive conductance; TWIK-1 knockout astrocytes show more negative resting potential and reduced inward rectification and Cs+ permeability without global change in passive conductance. Subcellular fractionation, TWIK-1 knockout mice, whole-cell patch-clamp in hippocampal slices Frontiers in cellular neuroscience High 24368895
2014 Native TWIK-1 forms a functional heterodimeric channel with TREK-1 at the plasma membrane of astrocytes via a disulfide bridge between Cys69 of TWIK-1 and Cys93 of TREK-1; surface expression of TWIK-1 and TREK-1 are interdependent; TWIK-1/TREK-1 heterodimers mediate astrocytic passive conductance and cannabinoid-induced glutamate release from astrocytes. Co-immunoprecipitation, gene silencing (shRNA), disulfide bond identification by mutagenesis, surface biotinylation, patch-clamp electrophysiology in native astrocytes Nature communications High 24496152
2014 TWIK-1 is expressed and localized mainly in 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 synaptic transmission. shRNA gene silencing, whole-cell patch-clamp in mouse hippocampal DGGCs, immunofluorescence Molecular brain High 25406588
2015 Lipid tails from both membrane leaflets can occupy fenestrations in the TWIK-1 pore and partially penetrate into the inner pore cavity; there is an inverse correlation between lipid tail occupancy and water content within the hydrophobic barrier, but dewetting (pore closure) also occurs in the absence of lipid tails, indicating that hydrophobic side chains lining the pore cavity are the primary determinant of the hydrophobic barrier. Molecular dynamics (MD) simulations based on TWIK-1 crystal structure Channels (Austin, Tex.) Medium 25487004
2015 mGluR3 activation (Gi/Go-coupled) triggers translocation of TWIK-1 channels from cytoplasm to the plasma membrane of hippocampal astrocytes via a Rab-mediated recycling endosome trafficking pathway; this membrane recruitment is associated with membrane depolarization and enhanced NH4+ uptake (~30% potentiation), a process absent in TWIK-1 knockout astrocytes. Live-cell imaging of TWIK-1 trafficking, electrophysiology (VM response to NH4Cl), TWIK-1 knockout comparison, pharmacological mGluR3 activation Molecular neurobiology Medium 26553349
2015 KCNK1 overexpression inhibits RANKL-induced osteoclast differentiation by attenuating Ca2+ oscillations and suppressing JNK activation and NFATc1 expression; conversely, KCNK1 knockdown enhances osteoclastogenesis, JNK activation and NFATc1 expression, placing KCNK1 as a negative regulator upstream of the Ca2+/JNK-NFATc1 axis. Overexpression and siRNA knockdown of KCNK1 in osteoclast precursors, Ca2+ imaging, immunoblotting for JNK/NFATc1, osteoclast differentiation assay Journal of cell science Medium 26208638
2016 MD simulations reveal that the TWIK-1 selectivity filter (SF) diverges from canonical K+ channel structure due to non-conserved residues T118 (pore domain 1) and L228 (pore domain 2); T118 behavior is linked to dynamic selectivity enabling Na+ influx at subphysiological K+ concentrations, consistent with inactivation-like SF gating. Molecular dynamics simulations (~1 µs cumulative) based on TWIK-1 crystal structure Biophysical journal Medium 27558721
2016 TWIK-1 is required for normal heart rate and atrial morphology in zebrafish; knockdown of kcnk1a or kcnk1b causes bradycardia and atrial dilation; the phenotype is partially rescued by wild-type human KCNK1 mRNA but not by a dominant-negative variant; zebrafish and human TWIK-1 channels show predominant localization in the endosomal compartment and produce K+ currents sensitive to external K+ concentration and acidic pH. Morpholino knockdown in zebrafish, mRNA rescue, two-electrode voltage-clamp in Xenopus oocytes, cellular localization by microscopy Journal of molecular and cellular cardiology High 27103460
2018 TWIK-1 associates with TASK-3 to form a heterodimeric channel in dentate gyrus granule cells (DGGCs) and in COS-7 cells; TWIK-1/TASK-3 heterodimers display outwardly rectifying currents and contribute to intrinsic excitability of DGGCs; neurotensin-neurotensin receptor 1 (NT-NTSR1) signaling depolarizes DGGCs by inhibiting TWIK-1/TASK-3 heterodimeric channels. Co-immunoprecipitation in hippocampal tissue and COS-7 cells, shRNA gene silencing, patch-clamp electrophysiology in DGGCs, pharmacological activation of NTSR1 Experimental & molecular medicine High 30416196
2019 The low intrinsic functional activity of TWIK-1 is dominated by instability of the conductive conformation of the selectivity filter (SF gate) in the presence of K+; Rb+, NH4+, and Cs+ promote a pH-dependent activated SF conformation; intracellular K+ potently inhibits TWIK-1 Rb+ currents (IC50 = 2.8 mM); voltage-dependent activation of TWIK-1 requires non-physiological strong depolarization. Patch-clamp electrophysiology with various permeant ions, systematic evaluation of proposed silencing mechanisms (sumoylation, internalization, hydrophobic barrier) using mutagenesis and pharmacology The Journal of biological chemistry High 31806709
2013 Nuclear receptor CAR directly binds a 97-bp response element (-2441/-2345) within the Kcnk1 promoter to drive male-specific transcription of Kcnk1 in mouse liver upon phenobarbital treatment; this activation requires the pituitary gland (abrogated by hypophysectomy); Kcnk1 knockout mice show enhanced phenobarbital-induced hepatic hyperplasia, establishing KCNK1 as a CAR-induced anti-hyperplasia factor. ChIP (CAR binding to Kcnk1 promoter), hypophysectomy experiment, Kcnk1 knockout mice with phenobarbital treatment, promoter reporter assay Toxicological sciences Medium 23291559
2020 Spadin (a TREK-1 inhibitor) dramatically reduces astrocytic passive conductance in brain slices; gene silencing demonstrates that spadin-sensitive currents are mediated by TWIK-1/TREK-1 heterodimeric channels in cultured astrocytes and hippocampal astrocytes from brain slices. Patch-clamp electrophysiology in brain slices and cultured astrocytes, shRNA gene silencing of TWIK-1 and/or TREK-1, pharmacology with spadin International journal of molecular sciences Medium 33348878
2021 AEG-1 (MTDH) binds directly to TWIK-1 mRNA and stabilizes it, thereby regulating TWIK-1 protein expression and TWIK-1-mediated K+ currents in astrocytes; AEG-1 knockdown downregulates TWIK-1 mRNA and protein, and reduces TWIK-1-mediated currents. RNA immunoprecipitation (AEG-1 binding to TWIK-1 mRNA), shRNA knockdown, qPCR, immunocytochemistry, patch-clamp electrophysiology Brain sciences Medium 33440655
2023 In the dorsal spinal horn, ciRNA-Kat6b acts as a sponge for miRNA-26a; nerve injury downregulates ciRNA-Kat6b, increasing free miRNA-26a which binds the 3'UTR of Kcnk1 mRNA and promotes its degradation, reducing KCNK1 protein and contributing to neuropathic pain; rescuing ciRNA-Kat6b restores KCNK1 and alleviates pain hypersensitivity. Luciferase reporter assay (miRNA-26a targeting Kcnk1 3'UTR), RNA immunoprecipitation (ciRNA-Kat6b/miRNA-26a interaction), Western blot, immunofluorescence, behavioral pain assays, CCI neuropathic pain model CNS neuroscience & therapeutics Medium 37144575
2024 KCNK1 promotes glycolysis and lactate production in breast cancer cells by directly binding to and activating LDHA; elevated LDHA activity promotes H3K18 lactylation and transcription of downstream genes including LDHA itself (positive feedback); this axis reduces tumor cell stiffness and adhesion, facilitating proliferation, invasion, and metastasis. Co-immunoprecipitation (KCNK1-LDHA binding), glycolysis/lactate assays, histone lactylation analysis (H3K18), in vitro invasion/proliferation assays, in vivo xenograft models PLoS biology Medium 38905316
2024 siRNA knockdown of KCNK1 in IPAH-PASMCs causes membrane depolarization, decreases cytosolic Ca2+, and suppresses proliferation and migration; elevated KCNK1 expression in IPAH-PASMCs facilitates proliferation and migration via enhanced Ca2+ signaling and elevated JNK phosphorylation. siRNA knockdown of KCNK1, patch-clamp electrophysiology, Ca2+ imaging, proliferation/migration assays, Western blot for pJNK, in IPAH patient-derived PASMCs and experimental PH animal models Frontiers in cardiovascular medicine Medium 38410243
2024 TWIK-1 (KCNK1) mediates K+ currents responsible for background passive conductance in astrocytes; TWIK-1 deficiency (exon 1 CRISPR-Cas9 knockout) increases susceptibility to kainic acid-induced seizures, demonstrating that TWIK-1-mediated astrocytic passive conductance has a neuroprotective role in seizure threshold. CRISPR-Cas9 exon 1 knockout mice, patch-clamp electrophysiology in astrocytes, kainic acid seizure model, comparison with exon 2-deleted (partial) KO iScience High 39811670

Source papers

Stage 0 corpus · 42 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 71 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 62 30416196
2019 Characterization of the in vitro, ex vivo, and in vivo Efficacy of the Antimicrobial Peptide DPK-060 Used for Topical Treatment. Frontiers in cellular and infection microbiology 57 31192163
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
2000 Cloning of DPK, a novel dendritic cell-derived protein kinase activating the ERK1/ERK2 and JNK/SAPK pathways. Biochemical and biophysical research communications 29 10924369
2015 Influence of lipids on the hydrophobic barrier within the pore of the TWIK-1 K2P channel. Channels (Austin, Tex.) 23 25487004
2019 Selectivity filter instability dominates the low intrinsic activity of the TWIK-1 K2P K+ channel. The Journal of biological chemistry 22 31806709
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
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 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 6 38410243
2024 Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer. European journal of medical research 6 38689322
2022 Design and pharmacodynamic evaluation of DPK-060 loaded Nanostructured lipid carrier embedded gel for dermal delivery: A novel approach in the treatment of atopic dermatitis. Colloids and surfaces. B, Biointerfaces 6 35810608
2024 A diffusion-leakage model coupled with dose point kernels (DPK) for dosimetry of diffusing alpha-emitters radiation therapy (DaRT). Medical physics 4 38284426
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
2012 SDS3 interacts with ARNT in an AhR ligand-specific manner regulating expression of cKrox and S100A4 in CD4+CD8+ DPK thymocytes differentiation. Environmental toxicology and pharmacology 2 22981438
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 0 41155507
2025 The preference for ammonium may be attributed to a hyperpolarized membrane potential via TWIK-1 channels. Brain research 0 41386584
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 0 39012638
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
2021 AEG-1 Regulates TWIK-1 Expression as an RNA-Binding Protein in Astrocytes. Brain sciences 0 33440655