Affinage

KCNK3

Potassium channel subfamily K member 3 · UniProt O14649

Length
394 aa
Mass
43.5 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNK3 (TASK-1) is a two-pore-domain background potassium channel that sets the resting membrane potential in pulmonary artery smooth muscle cells, cardiomyocytes, neurons, and immune cells, thereby controlling vascular tone, cardiac repolarization, neuronal excitability, and T cell effector function (PMID:14551239, PMID:21865850, PMID:19570851). Its surface expression depends on 14-3-3-mediated suppression of COPI-dependent ER retention and p11/annexin II binding to a C-terminal SSV motif, while PKC triggers 14-3-3β-dependent endocytic internalization (PMID:12198146, PMID:17908283, PMID:22846993). Channel gating is regulated by extracellular pH via histidine H98, by Gq-coupled GPCR signaling through a PLC→DAG pathway, by volatile anesthetics, and by an intramembrane X-gate (VLRFMT motif) that controls open probability and traps high-affinity inhibitors within the vestibule (PMID:12634929, PMID:25420509, PMID:32499642). Loss-of-function mutations or reduced expression cause pulmonary arterial hypertension and right ventricular dysfunction, whereas gain-of-function X-gate mutations produce overactive, GPCR-insensitive channels causing a developmental disorder with sleep apnea (PMID:31347976, PMID:36195757).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 High

    Establishing how GPCRs regulate TASK-1: Gq-coupled receptor inhibition of TASK-1 was shown to require PLC activity, ruling out direct G-protein or individual second-messenger mechanisms and identifying the PLC step as the obligate signal.

    Evidence Two-electrode voltage clamp in Xenopus oocytes with heterologous receptor expression and PLC inhibitor dissection

    PMID:11443069

    Open questions at the time
    • The precise downstream effector of PLC (PIP2 depletion vs. DAG vs. IP3) was not resolved
    • Mechanism in native cells not yet shown
  2. 2002 High

    Defining how TASK-1 reaches the plasma membrane: p11 was identified as a trafficking partner that masks a C-terminal ER retention signal (KRR) by binding the SSV motif, and H98 was identified as the principal extracellular pH sensor, establishing two fundamental regulatory axes — trafficking and gating.

    Evidence Co-immunoprecipitation and mutagenesis trafficking assays for p11; site-directed mutagenesis with two-electrode voltage clamp for H98

    PMID:12198146 PMID:12634929

    Open questions at the time
    • Whether p11 acts alone or requires 14-3-3 was unclear
    • Other residues contributing to pH sensing remained uncharacterized
  3. 2003 High

    Establishing TASK-1 as the physiological background K+ conductance in pulmonary vasculature and neurons: pharmacological profiling in native PASMCs and cerebellar granule neurons matched TASK-1, linking the channel to vascular tone and neuronal resting potential.

    Evidence Whole-cell patch clamp with TASK-1-selective pharmacological profiling in native rabbit PASMCs and rat cerebellar neurons

    PMID:12215606 PMID:14551239

    Open questions at the time
    • Molecular identity relied on pharmacological matching without genetic confirmation
    • Contribution of TASK-3 heterodimers not distinguished
  4. 2007 High

    Resolving the trafficking hierarchy: 14-3-3 binding was shown to be the primary mechanism suppressing COPI-mediated ER retention at both N- and C-terminal sites, with p11 acting downstream and modulatory; volatile anesthetics were characterized as direct TASK-1 activators at clinical concentrations.

    Evidence Pulldown and deletion mutant trafficking assays for 14-3-3/COPI; patch clamp with multiple anesthetics in oocytes and cardiomyocytes

    PMID:17699638 PMID:17908283

    Open questions at the time
    • Phosphorylation events governing 14-3-3 binding site accessibility not defined
    • Anesthetic binding site not structurally mapped
  5. 2009 High

    Delineating the full Gq signaling cascade in native cells and identifying TASK-1/TASK-3 heterodimers: ET-1 was shown to inhibit TASK-1 via ETA→PLC→DAG→PKC in human PASMCs, and single-channel recordings in carotid body identified functional TASK-1/TASK-3 heterodimers as the oxygen-sensitive conductance.

    Evidence Patch clamp with complete pharmacological pathway dissection and siRNA in hPASMCs; single-channel recording in native carotid body cells

    PMID:19188660 PMID:19403596

    Open questions at the time
    • Whether PKC acts directly on the channel or via an intermediary was not resolved
    • Heterodimer stoichiometry and regulation not determined
  6. 2010 High

    Expanding the regulatory landscape: PKG was found to modulate TASK-1 gating by altering H98-dependent proton affinity in basal forebrain neurons, and TASK-1 knockout mice revealed neuroprotective roles during ischemia and roles in thalamocortical firing mode transitions.

    Evidence Patch clamp with H98 mutagenesis and PKG modulators in native neurons and HEK293 cells; TASK-1 KO mice in MCAO ischemia model and brain slice recordings

    PMID:12878686 PMID:18930826 PMID:20410120

    Open questions at the time
    • PKG phosphorylation site on TASK-1 not identified
    • Relative contribution of TASK-1 vs TASK-3 in thalamocortical neurons not fully resolved
  7. 2012 High

    Distinguishing two modes of GPCR regulation — gating vs. trafficking: PKC was shown to drive 14-3-3β-dependent endocytic internalization of TASK-1 via a novel endocytic motif (acute trafficking regulation), while in cardiomyocytes ET-1 inhibited TASK-1 gating through PLC independently of PKC, indicating cell-type-specific regulatory mechanisms.

    Evidence Surface biotinylation and siRNA of 14-3-3β in cerebellar neurons; patch clamp with PKC/rho kinase inhibitors in rat cardiomyocytes

    PMID:22846993 PMID:22977011

    Open questions at the time
    • The endocytic motif sequence and its relationship to the 14-3-3 binding site not fully mapped
    • Whether trafficking and gating regulation co-occur in the same cell type unknown
  8. 2014 High

    Identifying DAG as the direct second messenger and linking channel phosphorylation to atrial fibrillation: DAG (not PIP2 depletion or IP3/Ca2+) was established as the signal mediating Gq-coupled GPCR inhibition of TASK channels, and phosphorylation-dependent TASK-1 loss of function was demonstrated in human AF tissue.

    Evidence DAG kinase/lipase manipulation with fluorescent reporters in heterologous cells; patch clamp with intracellular phosphatase rescue in human AF myocytes

    PMID:25420509 PMID:25437921

    Open questions at the time
    • The DAG binding site on TASK-1 not identified
    • The specific kinase and phosphorylation site responsible for AF-associated inhibition not determined
  9. 2016 High

    Establishing KCNK3 loss of function as a driver of pulmonary hypertension pathobiology: reduced KCNK3 expression/function in human PAH and animal models was shown to cause PASMC/endothelial proliferation, vasoconstriction, and inflammation, with in vivo pharmacological activation reversing experimental PH.

    Evidence Patch clamp in freshly isolated PASMCs, siRNA, monocrotaline rat model with pharmacological rescue

    PMID:26912814

    Open questions at the time
    • Mechanism of KCNK3 downregulation in PAH not established
    • Whether pharmacological activation is sufficient in genetic forms of PAH unknown
  10. 2019 High

    Genetic proof that KCNK3 loss causes spontaneous pulmonary hypertension: CRISPR-generated Kcnk3-null rats developed age-dependent PH with membrane depolarization, overactivation of ERK1/2, AKT, SRC, and HIF1-α overexpression, defining the downstream signaling cascade.

    Evidence CRISPR/Cas9 knockout rat with comprehensive hemodynamic, electrophysiological, and signaling pathway analysis

    PMID:31347976

    Open questions at the time
    • Whether the signaling cascade is a direct consequence of depolarization or involves KCNK3-specific protein interactions unknown
    • Therapeutic targeting of these downstream pathways not tested
  11. 2020 High

    Structural basis of gating and drug trapping resolved: the X-ray crystal structure revealed an intramembrane X-gate (VLRFMT at M4 helix crossing) that controls channel open probability; high-affinity inhibitors bind below the selectivity filter and are physically trapped by X-gate closure.

    Evidence X-ray crystallography with inhibitor co-crystal structures, validated by mutagenesis and electrophysiology

    PMID:32499642

    Open questions at the time
    • How GPCR signaling is transduced to the X-gate conformationally not determined
    • Structure of the open state not available
  12. 2022 High

    Gain-of-function X-gate mutations were shown to cause a developmental disorder with sleep apnea (DDSA), producing overactive channels insensitive to GPCR-mediated inhibition but still responsive to pharmacological blockers, establishing a new disease mechanism.

    Evidence Patch clamp and mutagenesis in heterologous systems with GPCR inhibition assays, published in Nature Genetics

    PMID:36195757

    Open questions at the time
    • Tissue-specific pathophysiology of GOF variants not characterized in vivo
    • Whether pharmacological rescue translates to therapeutic benefit untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for DAG-mediated channel inhibition, the conformational mechanism linking GPCR signaling to X-gate closure, the identity of the kinase and phosphorylation site underlying AF-associated TASK-1 inhibition, and whether combined pharmacological activation strategies can treat both LOF (PAH) and GOF (DDSA) KCNK3 channelopathies.
  • DAG binding site on TASK-1 unknown
  • Open-state channel structure unavailable
  • Phosphorylation site(s) mediating AF-associated inhibition not mapped
  • In vivo pharmacological rescue of GOF variants not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-382551 Transport of small molecules 4 R-HSA-1643685 Disease 3
Partners
KCNK17KCNK9S100A10YWHAB
Complex memberships
TASK-1/TASK-3 heterodimer

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 p11 (an annexin II subunit) interacts specifically with TASK-1 (KCNK3) via the last three C-terminal amino acids (Ser-Ser-Val), and this association is essential for trafficking of TASK-1 to the plasma membrane by masking an ER retention signal (Lys-Arg-Arg) that precedes the SSV sequence. Co-immunoprecipitation, C-terminal deletion mutants, TASK-1-GFP chimeras, heterologous expression The EMBO journal High 12198146
2001 TASK-1 (KCNK3) is inhibited by Gq-coupled receptor activation via a phospholipase C (PLC)-dependent mechanism; downstream signals IP3, Ca2+, and DAG do not individually mediate inhibition, and Gi-coupled receptors only inhibit TASK-1 when PLC-β2 is co-expressed, establishing PLC activity as the critical step. Two-electrode voltage clamp in Xenopus oocytes with heterologous receptor expression, GTPγS application, PLC inhibitor U-73122, receptor subtype dissection American journal of physiology. Cell physiology High 11443069
2003 TASK-1 mediates the noninactivating background K+ current (IKN) that sets the resting membrane potential in rabbit pulmonary artery smooth muscle cells; the current is inhibited by extracellular acidosis, Zn2+, anandamide, hypoxia, and enhanced by halothane, pharmacologically matching TASK-1 properties. Whole-cell patch clamp, RT-PCR, immunodetection in native PASMCs Circulation research High 14551239
2006 TASK-1 (KCNK3) controls resting membrane potential in human PASMCs; it is inhibited by hypoxia and activated by treprostinil through PKA-dependent phosphorylation; TASK-1 siRNA knockdown abolishes sensitivity to anandamide, acidosis, alkalosis, hypoxia, and treprostinil. Whole-cell patch clamp, siRNA knockdown, pharmacological dissection in primary human PASMCs Circulation research High 16574908
2007 Forward transport of KCNK3 (K2P3.1) to the plasma membrane requires 14-3-3-mediated suppression of COPI binding at two separate N- and C-terminal sites; p11 binding to the C-terminal retention motif is dependent on prior 14-3-3 binding and serves a modulatory role in a subset of tissues. Pulldown, co-immunoprecipitation, deletion mutants, heterologous expression trafficking assays Traffic (Copenhagen, Denmark) High 17908283
2009 TASK-1/TASK-3 heterodimeric channels constitute the major oxygen-sensitive background K+ conductance in rat carotid body glomus cells; single-channel conductance (~42 pS) and pharmacological profile (ruthenium red insensitivity, methanandamide sensitivity) distinguish heteromers from homodimers, and heterodimers are inhibited by hypoxia. Single-channel patch clamp (cell-attached and outside-out), manipulation of extracellular Mg2+, pharmacological profiling in native carotid body cells The Journal of physiology High 19403596
2002 Histidine residue H98 (and to a lesser extent H72 and K210) in TASK-1 contributes to extracellular pH sensing; mutating H98 significantly shifts the K_d for H+ block, though additional residues/domains also contribute to pH sensitivity. Site-directed mutagenesis, two-electrode voltage clamp in Xenopus oocytes Pflugers Archiv : European journal of physiology High 12634929
2002 TASK-1 mediates a standing outward K+ current in rat cerebellar granule neurons that sets resting membrane potential; hypoxia inhibits this TASK-1-mediated current causing neuronal depolarization, demonstrated by occlusion with pH 6.4 acidosis and anandamide. Whole-cell patch clamp in primary cerebellar granule neurons, pharmacological occlusion experiments Stroke High 12215606
2009 Endothelin-1 inhibits TASK-1 background K+ current in primary human PASMCs via ETA receptors coupled to phospholipase C, phosphatidylinositol 4,5-bisphosphate hydrolysis, diacylglycerol generation, and protein kinase C phosphorylation of TASK-1, causing membrane depolarization; TASK-1 siRNA abolishes ET-1 effect on membrane potential. Whole-cell patch clamp, siRNA knockdown, pharmacological inhibitors of ETA, PLC, PI(4,5)P2, DAG, PKC in primary hPASMCs American journal of respiratory cell and molecular biology High 19188660
2014 TASK-1 and TASK-3 channels are gated by diacylglycerol (DAG) downstream of Gαq/11-coupled GPCRs; receptor-initiated inhibition requires PLC activity and elevation of cellular DAG, but not PI(4,5)P2 depletion, IP3, or Ca2+ release; DAG kinase or lipase suppression of DAG transients blocks channel inhibition. Electrophysiology, DAG kinase/lipase manipulation, PI(4,5)P2 sensors, fluorescent DAG reporters, pharmacological dissection in heterologous cells Nature communications High 25420509
2012 Endothelin-1 inhibits TASK-1 current (ITASK) in rat cardiomyocytes via endothelin-A receptors and is mediated by PLC; inhibition is not affected by PKC or rho kinase inhibitors; TASK-1 inhibition by ET-1 prolongs action potential duration in cardiomyocytes. Whole-cell patch clamp in isolated rat cardiomyocytes, pharmacological inhibitors (U73122, PKC inhibitors, rho kinase inhibitors), TIRFM PI(4,5)P2 measurements Cardiovascular research High 22977011
2012 PKC-mediated endocytic trafficking dynamically regulates KCNK3 surface expression and activity; phorbol ester or group I mGluR activation acutely internalizes KCNK3 in a 14-3-3β-dependent manner requiring a novel endocytic motif on KCNK3; depletion of 14-3-3β or ablation of the endocytic motif abrogates PKC-regulated trafficking. Electrophysiology, surface biotinylation, siRNA depletion, endocytic motif mutagenesis in cerebellar granule neurons and cell lines The Journal of biological chemistry High 22846993
2020 TASK-1 (KCNK3) contains a lower gate (the 'X-gate') formed by the crossing of C-terminal M4 transmembrane helices (residues 243VLRFMT248); this gate controls channel open probability and responses to volatile anaesthetics and GPCRs; X-gate mutations affect gating, and high-affinity inhibitors bind below the selectivity filter and are trapped by the X-gate explaining slow washout. X-ray crystallography, mutagenesis, electrophysiology, inhibitor co-crystallization Nature High 32499642
2022 Gain-of-function mutations in KCNK3 cluster around the X-gate and produce overactive channels that no longer respond to inhibition by G-protein-coupled receptor pathways but can still be inhibited by known TASK channel inhibitors; these mutations cause a developmental disorder with sleep apnea (DDSA). Electrophysiology (patch clamp), mutagenesis in heterologous expression systems, GPCR inhibition assays Nature genetics High 36195757
2010 TASK1 and TASK3 channels in thalamocortical neurons contribute to the muscarine- and halothane-sensitive conductance; pharmacological blockade of TASK channels switches neurons from tonic to burst firing mode, demonstrating TASK1's role in regulating sleep-wake activity modes. Whole-cell patch clamp in rat brain slices, RT-PCR, in situ hybridization, pharmacological manipulation The Journal of neuroscience High 12878686
2010 TASK1 and TASK3 channels in brain slice preparations are inhibited by pH reduction and O2 deprivation, leading to membrane depolarization; pharmacological TASK blockade in vivo increases infarct volume in transient MCAO, and TASK1-/- mice develop significantly larger infarcts, demonstrating a neuroprotective role during ischemia. Patch clamp in brain slices, in vivo transient MCAO model, TASK1 knockout mice, pharmacological blockade (anandamide) Neurobiology of disease High 18930826
2010 PKG activation upregulates TASK-1 channels in cholinergic basal forebrain neurons by reducing H+ binding affinity (increasing K_d for protonation) at pH sensor H98; PKG inhibition has the opposite effect; this dynamic modulation was validated in HEK293 cells expressing PKG and TASK-1, and H98 mutation abolishes PKG modulation. Whole-cell patch clamp in basal forebrain neurons and HEK293 cells, H98 mutagenesis, pharmacological PKG activation/inhibition The Journal of neuroscience High 20410120
2019 Sp1 transcription factor controls p11 expression, and increased p11 promotes TASK-1 membrane insertion, reducing neuronal excitability in motor neurons; in the SOD1-G93A ALS mouse model, Sp1-p11-TASK-1 dysregulation contributes to motor neuron hyperexcitability and degeneration; interference with Sp1 or p11 is neuroprotective. In vivo ALS mouse model, genetic interference (siRNA/knockdown of Sp1 and p11), electrophysiology, survival analysis Nature communications High 31439839
2014 TASK-1 is inhibited by phosphorylation in chronic atrial fibrillation (human and canine); addition of phosphatase to the patch pipette rescues TASK-1 current from AF myocytes; total TASK-1 protein levels do not decrease, indicating post-translational phosphorylation-dependent loss of function rather than reduced expression. Whole-cell patch clamp with and without intracellular phosphatase, Western blot, tissue from human AF patients and chronically paced canines American journal of physiology. Heart and circulatory physiology High 25437921
2016 KCNK3 expression and function are reduced in human PAH and experimental pulmonary hypertension; loss of KCNK3 leads to pulmonary artery smooth muscle cell and endothelial cell proliferation, vasoconstriction, and inflammation; in vivo pharmacological activation of KCNK3 reverses monocrotaline-induced pulmonary hypertension in rats. Patch clamp in freshly isolated PASMCs, siRNA knockdown, monocrotaline rat PH model, in vivo pharmacological activation Circulation High 26912814
2017 Heterozygous KCNK3 mutations associated with PAH cause mutation-specific severity of channel dysfunction in both homomeric and heterodimeric channel configurations with KCNK9; KCNK9 co-assembly partially compensates for select KCNK3 mutations in tissues where both are expressed; ONO-RS-082 activates both wildtype and mutant KCNK3 causing hyperpolarization. Whole-cell patch clamp in human pulmonary artery smooth muscle cells and COS7 cells, engineered homomeric and heterodimeric mutant constructs Journal of the American Heart Association High 28889099
2019 Kcnk3-mutated rats (CRISPR/Cas9 94 bp deletion) lack KCNK3 current in pulmonary arterial smooth muscle cells; they develop spontaneous age-dependent pulmonary hypertension with plasma membrane depolarization, overactivation of ERK1/2, AKT, SRC, HIF1-α overexpression, reduced eNOS, impaired endothelial-derived hyperpolarizing factor, and increased susceptibility to experimental PH triggers. CRISPR/Cas9 knockout rat, patch clamp, echocardiography, hemodynamic measurements, signaling pathway analysis Circulation research High 31347976
2015 TASK1 modulates β-adrenergic response in brown adipocytes through the mineralocorticoid receptor (MR) pathway; Task1-null mice show impaired β3-adrenergic receptor response (reduced oxygen consumption, UCP1 expression, lipolysis) that is mimicked by corticoids and reversed by an MR inhibitor, indicating TASK1 controls thermogenic activity by modulating MR signaling. Task1-/- mouse model, brown adipocyte functional assays (OCR, UCP1, lipolysis), pharmacological MR modulation FASEB journal Medium 26527067
2003 GABAB receptor activation in rat carotid body type I cells activates a TASK-1-like background K+ conductance (anandamide- and Ba2+-sensitive) via Gi protein and PKA signaling (not PKC), providing presynaptic autoregulatory feedback that modulates hypoxia-induced chemosensory transmission. Patch clamp in carotid body cell clusters, GABAB receptor agonist/antagonist pharmacology, pertussis toxin, PKA inhibitor H-89 The Journal of physiology Medium 12949228
2017 TASK1 and TALK2, two K2P channels from different subfamilies, can heterodimerize in a pancreatic cell line and HEK293 cells; TASK1-TALK2 heterodimer currents show unique hybrid sensitivity to extracellular pH and halothane; co-expression of dominant-negative TALK2 reduces TASK1 currents. Single-molecule TIRF imaging, bimolecular fluorescence complementation, FRET, whole-cell patch clamp, tandem construct functional characterization PloS one Medium 29016681
2019 Doxapram inhibits human TASK-1 and TASK-3 channels equipotently (unlike rodent channels where it is selective for TASK-1); the inhibitory effect requires hydrophobic residues in the pore-lining region and the C-terminus of TASK-3; the positive enantiomer GAL-054 is more potent than doxapram. Whole-cell patch clamp in tsA201 cells expressing cloned human or mouse TASK channels, site-directed mutagenesis of pore-lining residues Acta physiologica Medium 31423744
2018 KCNK3 is predominantly expressed in adult rat right ventricular (RV) cardiomyocytes compared to left ventricular cardiomyocytes and participates in RV action potential repolarization; KCNK3 function is reduced prior to development of RV hypertrophy in multiple experimental PH models; chronic KCNK3 inhibition in rats induces RV hypertrophy, fibrosis, inflammation, and impaired RV function. Whole-cell patch clamp in isolated RV and LV cardiomyocytes, multiple rat PH models, pharmacological chronic KCNK3 inhibition with A293, echocardiography Cardiovascular research High 29360952
2019 miR-34a increases TASK-1 (KCNK3) expression and current in human iPSCs and decreases resting membrane potential in TASK-1-expressing Xenopus oocytes; miR-25, miR-21, miR-34a, and other miRNAs regulate KCNK3 expression in AF patients and are associated with atrial cardiomyopathy parameters. miRNA mimic/inhibitor transfection in human iPSCs, Western blot, two-electrode voltage clamp in Xenopus oocytes Journal of the American Heart Association Medium 35301863
2011 TASK-1 knockout mice display prolonged QTc interval and broadened QRS complex; TASK-1 current modulates action potential duration in ventricular cardiomyocytes; isoflurane slows heart rate and AV conduction in wild-type but not TASK-1-/- mice, demonstrating TASK-1 mediates isoflurane's cardiac electrophysiological effects. TASK-1 knockout mice, surface ECG, in vivo electrophysiological catheter protocol, action potential recordings, isoflurane challenge Cellular physiology and biochemistry High 21865850
2007 Volatile anesthetics (isoflurane enantiomers, sevoflurane, halothane) activate human TASK-1 at clinically relevant concentrations, whereas intravenous anesthetic etomidate inhibits TASK-1 (and TASK-3) in a concentration-dependent manner; propofol has no effect on TASK-1 or TASK-3. Whole-cell patch clamp in Xenopus oocytes and rat ventricular myocytes, pharmacological characterization of anesthetics American journal of physiology. Cell physiology High 17699638
2002 TASK-1 protein is localized to intercalated disks and the transverse-axial tubular network (T-tubules) in rat ventricular myocytes, as confirmed by detubulation with formamide; atrial myocytes show staining at intercalated disks with punctate T-tubule pattern. Western blot, immunofluorescence, formamide detubulation, RT-PCR in rat cardiac tissue American journal of physiology. Heart and circulatory physiology Medium 12063289
2024 KCNK3 knockdown in human pulmonary endothelial cells (hPECs) reduces migration, proliferation, and in vitro tubulogenesis, reduces caveolae number, and promotes mitochondrial membrane depolarization and glycolytic shift in hPASMCs; proximity labeling mass spectrometry identified the KCNK3 interactome across multiple cellular compartments; dasatinib decreases KCNK3 function/expression contributing to PA constriction. siRNA knockdown, proximity labeling + mass spectrometry (interactome), patch clamp, mitochondrial membrane potential assay, tube formation assay, caveolae quantification American journal of respiratory cell and molecular biology Medium 38546978
2015 TASK1 and TASK3 channels contribute to T lymphocyte effector function (cytokine production and proliferation); application of TASK blockers reduces outward current in CD3+ T cells by ~40% and inhibits IFN-γ production; TASK1-/- mice show impaired T cell proliferation/cytokine production and are protected from experimental autoimmune encephalomyelitis. Patch clamp on T lymphocytes, TASK1 knockout mice, EAE adoptive transfer model, pharmacological TASK blockade Brain: a journal of neurology High 19570851

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Screening for tumours in paraneoplastic syndromes: report of an EFNS task force. European journal of neurology 335 20880069
2009 Plasma membrane expansion: a neuron's Herculean task. Nature reviews. Neuroscience 210 19259102
2006 Impact of TASK-1 in human pulmonary artery smooth muscle cells. Circulation research 180 16574908
2010 Allotopic expression of mitochondrial-encoded genes in mammals: achieved goal, undemonstrated mechanism or impossible task? Nucleic acids research 172 20823090
2010 A complex task? Direct modulation of transcription factors with small molecules. Current opinion in chemical biology 165 20395165
2016 Potassium Channel Subfamily K Member 3 (KCNK3) Contributes to the Development of Pulmonary Arterial Hypertension. Circulation 154 26912814
2003 Two-pore domain K channel, TASK-1, in pulmonary artery smooth muscle cells. Circulation research 144 14551239
2003 Contribution of TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 channels to the control of activity modes in thalamocortical neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 143 12878686
2009 Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells. The Journal of physiology 128 19403596
2002 p11, an annexin II subunit, an auxiliary protein associated with the background K+ channel, TASK-1. The EMBO journal 128 12198146
1998 Aneuploidy: a report of an ECETOC task force. Mutation research 118 9587424
2005 Task-specific expression of the foraging gene in harvester ants. Molecular ecology 109 15723672
2001 Inhibition of TASK-1 potassium channel by phospholipase C. American journal of physiology. Cell physiology 93 11443069
2008 TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 critically influence T lymphocyte effector functions. The Journal of biological chemistry 90 18375952
2009 TASK1 modulates inflammation and neurodegeneration in autoimmune inflammation of the central nervous system. Brain : a journal of neurology 84 19570851
2015 TASK channels in arterial chemoreceptors and their role in oxygen and acid sensing. Pflugers Archiv : European journal of physiology 82 25623783
2019 Characterization of Kcnk3-Mutated Rat, a Novel Model of Pulmonary Hypertension. Circulation research 78 31347976
2014 Diacylglycerol mediates regulation of TASK potassium channels by Gq-coupled receptors. Nature communications 72 25420509
2020 A lower X-gate in TASK channels traps inhibitors within the vestibule. Nature 70 32499642
2011 Knock-out of the potassium channel TASK-1 leads to a prolonged QT interval and a disturbed QRS complex. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 69 21865850
2018 Loss of KCNK3 is a hallmark of RV hypertrophy/dysfunction associated with pulmonary hypertension. Cardiovascular research 63 29360952
2007 The TASK background K2P channels: chemo- and nutrient sensors. Trends in neurosciences 63 17945357
2010 From the background to the spotlight: TASK channels in pathological conditions. Brain pathology (Zurich, Switzerland) 62 20529081
2017 TASK-1 (KCNK3) channels in the lung: from cell biology to clinical implications. The European respiratory journal 61 29122916
2002 Hypoxic depolarization of cerebellar granule neurons by specific inhibition of TASK-1. Stroke 60 12215606
2002 Determinants of pH sensing in the two-pore domain K(+) channels TASK-1 and -2. Pflugers Archiv : European journal of physiology 60 12634929
2013 Genetic variation in the two-pore domain potassium channel, TASK-1, may contribute to an atrial substrate for arrhythmogenesis. Journal of molecular and cellular cardiology 59 24374141
2004 Photochemical genotoxicity: principles and test methods. Report of a GUM task force. Mutation research 58 14706512
2015 MicroRNA-mediated regulation of p21 and TASK1 cellular restriction factors enhances HIV-1 infection. Journal of cell science 57 25717002
2023 Explainable multi-task learning for multi-modality biological data analysis. Nature communications 55 37137905
2009 Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons. The European journal of neuroscience 54 19508695
2005 Differential expression of TASK channels between horizontal interneurons and pyramidal cells of rat hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 16207875
2003 GABA mediates autoreceptor feedback inhibition in the rat carotid body via presynaptic GABAB receptors and TASK-1. The Journal of physiology 54 12949228
2016 An homozygous mutation in KCNK3 is associated with an aggressive form of hereditary pulmonary arterial hypertension. Clinical genetics 51 27649371
2017 Nucleoside diphosphate and triphosphate prodrugs - An unsolvable task? Antiviral chemistry & chemotherapy 49 29096525
2019 RNA editing is abundant and correlates with task performance in a social bumblebee. Nature communications 48 30962428
2009 Endothelin-1 inhibits background two-pore domain channel TASK-1 in primary human pulmonary artery smooth muscle cells. American journal of respiratory cell and molecular biology 48 19188660
2007 Differential effects of volatile and intravenous anesthetics on the activity of human TASK-1. American journal of physiology. Cell physiology 47 17699638
2002 Expression of TASK-1, a pH-sensitive twin-pore domain K(+) channel, in rat myocytes. American journal of physiology. Heart and circulatory physiology 47 12063289
2013 A daunting task: manipulating leukocyte function with RNAi. Immunological reviews 46 23550647
2014 Overview of the gene ontology task at BioCreative IV. Database : the journal of biological databases and curation 45 25157073
2008 The neuroprotective impact of the leak potassium channel TASK1 on stroke development in mice. Neurobiology of disease 45 18930826
2001 KT3.2 and KT3.3, two novel human two-pore K(+) channels closely related to TASK-1. Journal of neurophysiology 42 11431495
2018 MODE-TASK: large-scale protein motion tools. Bioinformatics (Oxford, England) 41 29850770
2010 TASK1 and TASK3 potassium channels: determinants of aldosterone secretion and adrenocortical zonation. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 41 20049674
2014 Cloning, functional characterization, and remodeling of K2P3.1 (TASK-1) potassium channels in a porcine model of atrial fibrillation and heart failure. Heart rhythm 40 24952150
2014 Potent and selective inhibitors of the TASK-1 potassium channel through chemical optimization of a bis-amide scaffold. Bioorganic & medicinal chemistry letters 40 25017033
2011 Carvedilol targets human K2P 3.1 (TASK1) K+ leak channels. British journal of pharmacology 40 21410455
2007 Dorsal and ventral processing under dual-task conditions. Psychological science 37 17425526
2013 A gutsy task: generating intestinal tissue from human pluripotent stem cells. Digestive diseases and sciences 36 23532718
2023 Accelerated Chemical Reaction Optimization Using Multi-Task Learning. ACS central science 34 37252348
2012 The inhibition of the potassium channel TASK-1 in rat cardiac muscle by endothelin-1 is mediated by phospholipase C. Cardiovascular research 34 22977011
2015 The K+ channel TASK1 modulates β-adrenergic response in brown adipose tissue through the mineralocorticoid receptor pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 26527067
2007 Forward Transport of K2p3.1: mediation by 14-3-3 and COPI, modulation by p11. Traffic (Copenhagen, Denmark) 32 17908283
2016 Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders. Human genomics 31 27353043
2019 Dissociating task acquisition from expression during learning reveals latent knowledge. Nature communications 29 31089133
2016 KCNK3 Variants Are Associated With Hyperaldosteronism and Hypertension. Hypertension (Dallas, Tex. : 1979) 29 27296998
2022 MicroRNAs Regulate TASK-1 and Are Linked to Myocardial Dilatation in Atrial Fibrillation. Journal of the American Heart Association 28 35301863
2017 The Impact of Heterozygous KCNK3 Mutations Associated With Pulmonary Arterial Hypertension on Channel Function and Pharmacological Recovery. Journal of the American Heart Association 28 28889099
2012 KCNE Regulation of K(+) Channel Trafficking - a Sisyphean Task? Frontiers in physiology 28 22754540
2021 Modeling multi-species RNA modification through multi-task curriculum learning. Nucleic acids research 27 33744973
2010 Expression of the kcnk3 potassium channel gene lessens the injury from cerebral ischemia, most likely by a general influence on blood pressure. Neuroscience 26 20167264
2023 Combatting persister cells: The daunting task in post-antibiotics era. Cell insight 25 37304393
2020 Vitamin D deficiency downregulates TASK-1 channels and induces pulmonary vascular dysfunction. American journal of physiology. Lung cellular and molecular physiology 24 32726132
2020 Down-regulation of lncRNA Gas5 promotes hypoxia-induced pulmonary arterial smooth muscle cell proliferation by regulating KCNK3 expression. European journal of pharmacology 24 33010302
2019 Sp1-regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1. Nature communications 24 31439839
2022 KCNK3 inhibits proliferation and glucose metabolism of lung adenocarcinoma via activation of AMPK-TXNIP pathway. Cell death discovery 23 35963847
2022 Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea. Nature genetics 23 36195757
2014 Basal forebrain moderates the magnitude of task-dependent amygdala functional connectivity. Social cognitive and affective neuroscience 23 24847112
2014 Task relevance regulates the interaction between reward expectation and emotion. Experimental brain research 21 24553754
2014 KCNK3: new gene target for pulmonary hypertension? Expert review of respiratory medicine 20 24742047
2021 Current Drug Treatment Strategies for Atrial Fibrillation and TASK-1 Inhibition as an Emerging Novel Therapy Option. Frontiers in pharmacology 19 33897427
2020 Epigenetics explained: a topic "primer" for the epilepsy community by the ILAE Genetics/Epigenetics Task Force. Epileptic disorders : international epilepsy journal with videotape 19 32301721
2020 Proteomic Analysis of KCNK3 Loss of Expression Identified Dysregulated Pathways in Pulmonary Vascular Cells. International journal of molecular sciences 19 33036472
2019 Effects of the ventilatory stimulant, doxapram on human TASK-3 (KCNK9, K2P9.1) channels and TASK-1 (KCNK3, K2P3.1) channels. Acta physiologica (Oxford, England) 19 31423744
2019 Antiarrhythmic Properties of Ranolazine: Inhibition of Atrial Fibrillation Associated TASK-1 Potassium Channels. Frontiers in pharmacology 19 32038227
2016 Controlling DNA-End Resection: An Emerging Task for Ubiquitin and SUMO. Frontiers in genetics 19 27602047
2024 Hemoadsorption therapy for myoglobin removal in rhabdomyolysis: consensus of the hemoadsorption in rhabdomyolysis task force. BMC nephrology 18 39085790
2021 Rodent mnemonic similarity task performance requires the prefrontal cortex. Hippocampus 18 33606338
2021 Task-induced modulations of neuronal activity along the auditory pathway. Cell reports 18 34910908
2020 Timing of response onset and offset in macaque V4: stimulus and task dependence. Journal of neurophysiology 18 32401171
2012 Implicit motives, explicit traits, and task and contextual performance at work. The Journal of applied psychology 18 22867444
2012 Modulation of K2P3.1 (TASK-1), K2P9.1 (TASK-3), and TASK-1/3 heteromer by reactive oxygen species. Pflugers Archiv : European journal of physiology 18 23007462
2010 Nuclear shield: a multi-enzyme task-force for nucleus protection. PloS one 18 21170318
2020 Inhibition of RELM-β prevents hypoxia-induced overproliferation of human pulmonary artery smooth muscle cells by reversing PLC-mediated KCNK3 decline. Life sciences 17 32045592
2014 Emotional task management: neural correlates of switching between affective and non-affective task-sets. Social cognitive and affective neuroscience 17 25552571
2010 Protein kinase G dynamically modulates TASK1-mediated leak K+ currents in cholinergic neurons of the basal forebrain. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 20410120
2021 KCNK3 Mutation Causes Altered Immune Function in Pulmonary Arterial Hypertension Patients and Mouse Models. International journal of molecular sciences 16 34065088
2017 MicroRNA‑138 promotes proliferation and suppresses mitochondrial depolarization in human pulmonary artery smooth muscle cells through targeting TASK‑1. Molecular medicine reports 16 29257242
2016 pH-dependent inhibition of K₂P3.1 prolongs atrial refractoriness in whole hearts. Pflugers Archiv : European journal of physiology 16 26729267
2014 TASK-1 current is inhibited by phosphorylation during human and canine chronic atrial fibrillation. American journal of physiology. Heart and circulatory physiology 16 25437921
2012 BioNLP Shared Task--The Bacteria Track. BMC bioinformatics 16 22759457
2012 The acid-sensitive, anesthetic-activated potassium leak channel, KCNK3, is regulated by 14-3-3β-dependent, protein kinase C (PKC)-mediated endocytic trafficking. The Journal of biological chemistry 16 22846993
2023 Physiological and pathophysiological roles of the KCNK3 potassium channel in the pulmonary circulation and the heart. The Journal of physiology 15 37477289
2020 Preoperative staging of the mediastinum is an essential and multidisciplinary task. Respirology (Carlton, Vic.) 15 32656946
2006 TASK channel expression in human placenta and cytotrophoblast cells. Journal of the Society for Gynecologic Investigation 15 16378911
2024 Role of KCNK3 Dysfunction in Dasatinib-associated Pulmonary Arterial Hypertension and Endothelial Cell Dysfunction. American journal of respiratory cell and molecular biology 14 38546978
2022 ProteinGLUE multi-task benchmark suite for self-supervised protein modeling. Scientific reports 14 36163232
2017 Heterodimerization of two pore domain K+ channel TASK1 and TALK2 in living heterologous expression systems. PloS one 14 29016681
2010 Targeting TASK-1 channels as a therapeutic approach. Advances in experimental medicine and biology 14 20204749