Affinage

Showing KCNJ8 — KIR6.1 is a alias.

KCNJ8

ATP-sensitive inward rectifier potassium channel 8 · UniProt Q15842

Length
424 aa
Mass
48.0 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNJ8 encodes Kir6.1, the pore-forming inward-rectifier subunit of vascular and smooth-muscle ATP-sensitive (KATP) channels that couples cellular metabolic state to membrane potential and thereby controls vascular tone and smooth-muscle contractility (PMID:9130167, PMID:11984590). Kir6.1 assembles with sulfonylurea receptor subunits—primarily SUR2B in vascular smooth muscle and SUR1 in neurons and astrocytes—to form channels activated by nucleotide diphosphates and K+ channel openers (pinacidil, nicorandil) and blocked by glibenclamide; unlike Kir6.2, the Kir6.1 pore is not directly inhibited by intracellular ATP, with metabolic (ATP) sensitivity instead conferred by the nucleotide-binding domains of SUR2B (PMID:9130167, PMID:8865068, PMID:18522960). Channel activity is dynamically tuned by PKC, which inhibits Kir6.1/SUR2B by phosphorylating a cluster of distal C-terminal serines, a route exploited by Gq-coupled vasoconstrictors such as arginine vasopressin (PMID:12015420, PMID:18048350, PMID:17428891). Knockout mice establish Kir6.1 as the obligate vascular KATP subunit: loss produces coronary vasospasm, ST elevation and sudden death, predisposes to fatal endotoxic shock, and raises blood pressure, whereas smooth-muscle gain-of-function lowers blood pressure and impairs contractility across vascular, lymphatic and intestinal smooth muscle (PMID:11984590, PMID:17077304, PMID:23974906, PMID:32372450, PMID:33170808). Kir6.1 additionally governs brain vascular smooth-muscle differentiation through Ca2+ oscillation control (PMID:35588738) and, in neurons and astrocytes, Kir6.1/SUR1 channels act as glucose/metabolic sensors that suppress glutamate release and seizure activity (PMID:17883401, PMID:10050011). Gain-of-function missense mutations that reduce ATP sensitivity and stabilize the open state (S422L, C176S, V65M, A88G) cause J-wave/early-repolarization arrhythmia syndromes and Cantú syndrome, while loss-of-function variants (E332del, V346I) are associated with SIDS (PMID:20558321, PMID:22056721, PMID:24700710, PMID:28842488, PMID:21836131, PMID:41995661). Beyond its channel activity, Kir6.1 exerts ion-conduction-independent functions, directly binding NLRP3 to restrain inflammasome assembly in metabolic and neuroinflammatory contexts (PMID:31387986, PMID:33838249, PMID:36185602).

Mechanistic history

Synthesis pass · year-by-year structured walk · 36 steps
  1. 1996 High

    Established that Kir6.1 is not an autonomous channel but requires a sulfonylurea-receptor partner, since SUR1 co-expression was needed to confer diazoxide and ATP sensitivity.

    Evidence Whole-cell patch-clamp of Kir6.1 alone versus Kir6.1+SUR1 in HEK293 cells

    PMID:8865068

    Open questions at the time
    • Did not establish the physiological SUR partner in native tissues
    • Channel stoichiometry not resolved
  2. 1997 High

    Defined Kir6.1/SUR2B as a nucleotide-diphosphate-activated channel pharmacologically distinct from the classical ATP-inhibited Kir6.2 channel, resolving its activation logic.

    Evidence Patch-clamp of HEK293T cells co-transfected with SUR2B and Kir6.1 with multiple pharmacological manipulations

    PMID:9130167

    Open questions at the time
    • Mechanism of ATP-independence not localized to a specific subunit
    • Native channel composition not yet confirmed
  3. 1997 Medium

    First subcellular-localization claim placed Kir6.1 at the mitochondrial inner membrane, proposing it as the mitochondrial KATP subunit.

    Evidence Immunoblot of subcellular fractions, immunofluorescence and immunoelectron microscopy with anti-Kir6.1 antibody in rat tissues

    PMID:9434770

    Open questions at the time
    • Antibody specificity not validated by orthogonal protein identification
    • Later contradicted by mass spectrometry
  4. 2002 High

    Genetically proved Kir6.1 is the pore-forming subunit of the vascular KATP channel and that its loss causes coronary vasospasm and sudden death, anchoring its physiological role in vascular tone.

    Evidence Kir6.1 knockout mice with ECG, vascular smooth muscle patch-clamp, and pharmacological vasodilation assays

    PMID:11984590

    Open questions at the time
    • Did not define SUR partner in vivo
    • Did not address non-vascular tissues
  5. 2001 High

    Extended Kir6.1's role beyond vasculature by identifying it as the principal KATP pore subunit in astrocytes, localized to perisynaptic processes.

    Evidence Subunit-specific immunocytochemistry, immunoelectron microscopy, and slice patch-clamp in Bergmann glia

    PMID:11749042

    Open questions at the time
    • Functional consequence for neurotransmission not yet shown
    • SUR partner identity in astrocytes not resolved here
  6. 2007 High

    Overturned the mitochondrial-localization claim by showing the immunoreactive bands attributed to Kir6.1 in heart mitochondria are metabolic enzymes, removing support for Kir6.1 as the mitoKATP subunit.

    Evidence LC-MS/MS protein identification from purified heart mitochondrial fractions with native/2D gels

    PMID:18068667

    Open questions at the time
    • Did not establish the true localization of Kir6.1
    • Negative result for one tissue does not exclude mitochondrial Kir6.1 elsewhere
  7. 2000 High

    Functionally tested subunit composition, showing Kir6.1 and Kir6.2 do not heteromultimerize in native cardiac myocytes and that Kir6.2 is the cardiac surface pore subunit.

    Evidence Adenoviral dominant-negative gene transfer and whole-cell patch-clamp in A549 cells and rabbit ventricular myocytes

    PMID:10837494

    Open questions at the time
    • Conflicts with biochemical evidence of Kir6.1/Kir6.2 heteromers in some systems
    • Did not address endothelial heteromeric assemblies
  8. 2002 High

    Identified differential PKC regulation as a defining signature of the Kir6.1/SUR2B vascular channel, linking it to native KNDP channels.

    Evidence Patch-clamp of reconstituted channels with purified PKC and pharmacological controls in HEK293 cells

    PMID:12015420

    Open questions at the time
    • Specific phosphorylation sites not yet mapped
    • Upstream physiological PKC activators not defined here
  9. 2007 High

    Mapped PKC inhibition to a defined cluster of distal C-terminal serines, providing the molecular substrate of vasoconstrictor signaling onto the channel.

    Evidence Kir6.1-Kir6.2 chimeras, serine-to-alanine mutagenesis, patch-clamp, and in vitro 32P phosphorylation with purified PKC

    PMID:18048350

    Open questions at the time
    • Phosphorylation stoichiometry in vivo not determined
    • Structural basis of how phosphorylation alters gating not resolved
  10. 2007 High

    Connected the PKC pathway to a physiological vasoconstrictor by showing arginine vasopressin inhibits the channel through V1a receptor/PKC, lowering open probability.

    Evidence Patch-clamp in HEK293 co-expressing Kir6.1/SUR2B and V1a receptor plus isolated mesenteric artery recordings

    PMID:17428891

    Open questions at the time
    • Did not map the AVP-targeted residues directly
    • Other Gq agonists not tested
  11. 2008 High

    Resolved the source of metabolic sensitivity, attributing ATP regulation to the SUR2B nucleotide-binding domains rather than the Kir6.1 pore.

    Evidence 86Rb efflux and patch-clamp in HEK293/CHO cells with SUR2B NBD mutagenesis

    PMID:18522960

    Open questions at the time
    • Did not determine NBD nucleotide-binding kinetics
    • Coupling between NBD occupancy and pore gating not structurally defined
  12. 1999 High

    Showed Kir6.1 reciprocally modulates SUR2B pharmacology by increasing glibenclamide affinity, demonstrating the pore subunit shapes drug sensitivity of the complex.

    Evidence Radioligand binding and whole-cell voltage-clamp in transfected HEK cells

    PMID:10531400

    Open questions at the time
    • Structural basis of affinity shift not addressed
    • Effect on other sulfonylureas not tested
  13. 2010 High

    Identified gain-of-function as a disease mechanism by linking the S422L mutation to increased cardiac KATP current and J-wave syndromes.

    Evidence Site-directed mutagenesis, heterologous expression with SUR2A, whole-cell patch-clamp in COS-1 cells

    PMID:20558321

    Open questions at the time
    • Biophysical basis of the current increase not yet defined
    • In vivo arrhythmia mechanism not modeled
  14. 2011 High

    Defined the biophysical basis of S422L gain-of-function as markedly reduced ATP sensitivity causing incomplete channel closure, and replicated the J-wave association.

    Evidence Whole-cell and inside-out patch-clamp of KCNJ8 variants with SUR2A in TSA201 cells with direct sequencing

    PMID:22056721

    Open questions at the time
    • In vivo cardiac phenotype not directly tested
    • Penetrance and modifier effects unaddressed
  15. 2011 High

    Demonstrated bidirectional disease genetics by linking KCNJ8 loss-of-function variants to SIDS via reduced KATP current.

    Evidence ORF sequencing of a 292-case SIDS cohort with heterologous expression and patch-clamp of mutants

    PMID:21836131

    Open questions at the time
    • Causality in individual SIDS cases not established
    • Tissue-specific consequence of LOF not modeled in vivo
  16. 2014 High

    Established KCNJ8 as a causal Cantú syndrome gene, identifying gain of KATP function (reduced ATP sensitivity) as the cardinal mechanism independent of SUR partner.

    Evidence Candidate gene screening and patch-clamp of Kir6.1[C176S] with SUR1 or SUR2A plus ATP sensitivity assays

    PMID:24700710

    Open questions at the time
    • Tissue-specific contribution to the multisystem phenotype not dissected here
    • Structural mechanism of reduced ATP sensitivity not resolved
  17. 2017 High

    Localized a conserved gating element by showing the slide-helix V65M Cantú mutation stabilizes the open state and reduces both ATP and glibenclamide sensitivity, predicting sulfonylurea resistance.

    Evidence 86Rb efflux and patch-clamp of V65M/V65L mutants in Kir6.1 and Kir6.2 with multiple SUR partners

    PMID:28842488

    Open questions at the time
    • Therapeutic alternative to sulfonylurea not identified
    • Atomic structure of slide-helix gating not solved here
  18. 2026 High

    Defined a new gain-of-function variant (A88G) with increased single-channel conductance and provided a structural-dynamics mechanism via selectivity-filter widening.

    Evidence Whole-cell/inside-out patch-clamp, single-channel analysis, homology modelling and molecular dynamics in HEK293 cells

    PMID:41995661

    Open questions at the time
    • Structural prediction not experimentally validated by cryo-EM
    • Clinical penetrance not established
  19. 2006 High

    Connected Kir6.1 to systemic metabolic stress response by showing its loss predisposes mice to fatal endotoxic shock through failed coronary vasodilation.

    Evidence Kir6.1 KO mice in an LPS endotoxin model with survival analysis and K+ channel opener rescue

    PMID:17077304

    Open questions at the time
    • Did not define the upstream metabolic signal sensed
    • Cell-autonomous versus systemic contributions not separated
  20. 2009 High

    Identified transcriptional upregulation of Kir6.1/SUR2B by LPS via NF-κB as a mechanism linking inflammation to vasodilation.

    Evidence Mesenteric ring contractility, patch-clamp of aortic myocytes, qPCR and NF-κB inhibitor validation

    PMID:19959479

    Open questions at the time
    • Direct NF-κB binding to the KCNJ8 promoter not shown
    • Relevance to chronic inflammation untested
  21. 2020 High

    Identified post-transcriptional control of Kir6.1 by miR-223 directly targeting its 3'UTR, linking the reactive carbonyl methylglyoxal to enhanced vasoconstriction.

    Evidence miR-223 gain/loss, luciferase 3'UTR reporter with mutagenesis, patch-clamp and mesenteric ring assays

    PMID:32151743

    Open questions at the time
    • In vivo relevance to diabetic vasculopathy not established
    • Other miRNAs regulating KCNJ8 not surveyed
  22. 2013 High

    Established a direct causal link between Kir6.1 channel activity in smooth muscle and blood pressure, with gain-of-function lowering and loss raising pressure.

    Evidence Tamoxifen-inducible smooth-muscle-specific gain- and loss-of-function transgenic mice with telemetry, contractility, and myocyte patch-clamp

    PMID:23974906

    Open questions at the time
    • Did not address renal/endothelial contributions to blood pressure
    • Long-term cardiovascular remodeling not assessed
  23. 2022 High

    Revealed a developmental role: Kir6.1/ABCC9 cell-autonomously drives brain vascular smooth-muscle differentiation through Ca2+ oscillation control via voltage-dependent Ca channels.

    Evidence Kcnj8 KO mice, zebrafish inhibition, cell culture, and Ca2+ imaging with channel manipulation

    PMID:35588738

    Open questions at the time
    • Transcriptional program downstream of Ca2+ oscillations not mapped
    • Human relevance to Cantú vascular phenotype not directly tested
  24. 1999 High

    Identified Kir6.1/SUR1 as the glucose-sensing KATP channel in ventromedial hypothalamic neurons, extending Kir6.1 to central metabolic sensing.

    Evidence Brain slice patch-clamp with single-cell RT-PCR and pharmacological/leptin manipulation

    PMID:10050011

    Open questions at the time
    • Behavioral consequences of channel modulation not tested
    • Stoichiometry of neuronal Kir6.1/SUR1 not defined
  25. 2007 High

    Showed Kir6.1/SUR1 at hippocampal presynaptic terminals suppresses glutamate release and seizure susceptibility, defining a neuroprotective synaptic role.

    Evidence Immunofluorescence co-localization, glutamate-release patch-clamp in KO mice, and seizure susceptibility assays

    PMID:17883401

    Open questions at the time
    • Metabolic trigger for presynaptic channel opening in vivo not defined
    • Contribution to human epilepsy untested
  26. 2016 High

    Demonstrated Kir6.1 can be incorporated into pancreatic β-cell KATP channels, with gain-of-function impairing insulin secretion and causing diabetes.

    Evidence β-cell-specific Kir6.1 GoF transgenic mice, glucose tolerance and insulin secretion assays, qRT-PCR of native islet transcripts

    PMID:27956473

    Open questions at the time
    • Native Kir6.1 contribution to physiological insulin secretion not quantified
    • SUR partner in β-cell Kir6.1 channels not defined
  27. 2020 High

    Extended the smooth-muscle KATP role to lymphatics, showing Kir6.1/SUR2B controls lymphatic contractility specifically in smooth muscle, not endothelium.

    Evidence PCR subunit identification, pressure myography, KO and cell-type-specific GoF transgenic mice with glibenclamide rescue

    PMID:32372450

    Open questions at the time
    • Physiological lymphatic stimuli regulating the channel not defined
    • Relevance to human lymphedema untested
  28. 2020 High

    Demonstrated Kir6.1/SUR2 KATP channels govern gastrointestinal smooth-muscle contractility and that Cantú gain-of-function causes dysmotility rescuable by glibenclamide.

    Evidence Kir6.1/SUR2 KO and human CS-mutation knockin mice with intestinal contractility, GI transit, and glibenclamide treatment

    PMID:33170808

    Open questions at the time
    • Cell-type within the gut wall responsible not isolated
    • Long-term motility consequences not assessed
  29. 2026 Medium

    Proposed a constitutively active Kir6.1 cardiac KATP channel distinct from Kir6.2/SUR2A that mediates adenosine- and preconditioning-induced cardioprotection and sex differences.

    Evidence Patch-clamp of isolated cardiomyocytes, adenosine/preconditioning protocols, coronary ligation and Ca2+ measurements

    PMID:42088949

    Open questions at the time
    • Single lab and novel finding awaiting independent confirmation
    • Molecular composition of the cardiac Kir6.1 channel not defined
    • Conflicts with earlier evidence excluding Kir6.1 from cardiac surface channels
  30. 2024 Medium

    Revealed an immune developmental role, with Kir6.1 required for normal NK cell maturation and a functional PNU-37883A-sensitive current in NK cells.

    Evidence NK cell-specific Kcnj8 KO mice with flow cytometry, patch-clamp, and transcriptomics

    PMID:39687626

    Open questions at the time
    • Single lab; mechanism linking channel activity to maturation unknown
    • SUR partner in NK cells not identified
  31. 2012 Medium

    Identified Cx43 as a phospho-specific Kir6.1 interaction partner, with phosphorylation at Cx43-Ser262 required for binding.

    Evidence Pulldown, co-immunoprecipitation, co-localization and phospho-deficient mutagenesis

    PMID:22960107

    Open questions at the time
    • Single lab; reciprocal validation and physiological role not established
    • Subcellular site of interaction not confirmed
  32. 2014 Medium

    Extended the Cx43 interaction to a functional anti-apoptotic role under hypoxia mediated by PKCε.

    Evidence Co-IP, co-localization, PKC inhibitor studies and hypoxia apoptosis assays in H9C2 cardiomyocytes

    PMID:24815185

    Open questions at the time
    • Mitochondrial localization claim contested
    • Single lab and cell-line only
  33. 2019 Medium

    Defined an ion-channel-independent function: Kir6.1 directly binds NLRP3 to suppress inflammasome assembly, with loss worsening insulin resistance.

    Evidence Endogenous Kir6.1-NLRP3 co-IP, KO/overexpression in mice and primary cells, inflammasome and insulin resistance assays

    PMID:31387986

    Open questions at the time
    • Single lab; binding interface not mapped
    • Whether suppression requires channel structure or conduction not separated
  34. 2018 Medium

    Linked Kir6.1 to neuroinflammation by showing its deficiency promotes microglial M1 polarization and p38 MAPK-NF-κB signaling, exacerbating dopaminergic neuron death.

    Evidence Kir6.1 knockdown/overexpression in microglia, MPTP KO PD model, and p38 MAPK inhibitor in vivo rescue

    PMID:29540778

    Open questions at the time
    • Single lab; molecular link between Kir6.1 and p38 signaling unknown
    • Channel-dependence of the effect not established
  35. 2019 Medium

    Showed astrocytic Kir6.1 maintains mitophagy, preventing damaged-mitochondria accumulation, ROS, and neuroinflammation in Parkinson models.

    Evidence Astrocyte-specific Kir6.1 KO mice in MPTP model with mitophagy and ROS assays plus mitophagy rescue

    PMID:31288070

    Open questions at the time
    • Single lab; mechanism by which Kir6.1 regulates mitophagy unknown
    • Channel versus non-channel role not distinguished
  36. 2022 Medium

    Consolidated the Kir6.1-NLRP3 axis in CNS, showing astrocytic Kir6.1 restrains NLRP3 inflammasome/pyroptosis to protect against neurodegeneration and depressive-like behavior.

    Evidence Astrocyte-specific Kir6.1 KO mice, co-IP of Kir6.1-NLRP3, inflammasome assays, and NF-κB/C3aR/VX-765 rescues across PD and depression models

    PMID:33838249 PMID:36185602

    Open questions at the time
    • Single lab studies; structural basis of NLRP3 binding unresolved
    • Relationship between channel activity and inflammasome inhibition unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of Kir6.1/SUR assembly and gating, the definitive subcellular localization (ER versus mitochondria versus plasma membrane), and the mechanistic boundary between Kir6.1's channel and channel-independent (NLRP3, mitophagy) functions remain unresolved.
  • No experimental atomic structure of Kir6.1/SUR in the corpus
  • Localization claims (mitochondria, ER, plasma membrane) remain contradictory
  • Whether NLRP3 suppression requires conducting channel or only the protein is undetermined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0098772 molecular function regulator activity 2 GO:0140299 molecular sensor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-382551 Transport of small molecules 2
Partners
ABCC9CFTRCX43KIR6.2NLRP3SUR1SUR2ASUR2B
Complex memberships
KATP channel (Kir6.1/SUR1)KATP channel (Kir6.1/SUR2B)

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Kir6.1 forms a functional K+ channel with SUR2B that is activated by nucleotide diphosphates (UDP, GDP) and K+ channel openers (pinacidil, nicorandil), inhibited by glibenclamide, but not inhibited by intracellular ATP alone — making it an NDP-dependent rather than classical ATP-sensitive K+ channel. Intracellular ATP on its own activated rather than inhibited the channel. Patch-clamp electrophysiology (cell-attached and inside-out configurations) in HEK293T cells co-transfected with SUR2B and Kir6.1 The Journal of physiology High 9130167
1996 SUR1 is required to confer both diazoxide sensitivity and ATP sensitivity on Kir6.1; Kir6.1 expressed alone in HEK293 cells shows currents unaffected by diazoxide or intracellular ATP, but Kir6.1+SUR1 co-expression produces diazoxide-activated and ATP-regulated currents. Whole-cell patch-clamp in HEK293 cells transfected with Kir6.1 alone or co-transfected with Kir6.1 and SUR1 The Journal of physiology High 8865068
2002 Kir6.1 knockout mice develop spontaneous ST elevation, atrioventricular block, and sudden death resembling Prinzmetal angina; vascular smooth muscle cells from knockout mice lack pinacidil-induced K+ currents and vasodilation, establishing Kir6.1 as the pore-forming subunit of the vascular KATP channel critical for coronary artery tone regulation. Gene knockout mouse model; patch-clamp of vascular smooth muscle cells; ECG recordings; pharmacological vasodilation assays; methylergometrine challenge Nature medicine High 11984590
1997 Kir6.1 protein localizes predominantly to mitochondria (inner membrane) in rat skeletal muscle, cardiac muscle, liver, and pancreas, as well as weakly to plasma membrane, suggesting it may be a subunit of the mitochondrial ATP-sensitive K+ channel. Immunoblot of subcellular fractions, immunofluorescence staining, and immunoelectron microscopy with anti-Kir6.1 antibody Biochemical and biophysical research communications Medium 9434770
2007 Antibody-based immunoblot signals previously attributed to Kir6.1 in heart mitochondria were identified by LC-MS/MS as NADH-dehydrogenase flavoprotein 1 (51 kDa band) and mitochondrial isocitrate dehydrogenase (48 kDa band), not Kir6.1; these results argue against Kir6.1 being a subunit of the mitochondrial KATP channel based on immunoreactivity alone. Immunoblot, immunogold electron microscopy, immunofluorescence, 1D/2D/native gel, LC-MS/MS protein identification from isolated heart mitochondria Biochemical and biophysical research communications High 18068667
2001 Kir6.1 (not Kir6.2) is the principal pore-forming subunit of KATP channels in astrocytes, localizing to distal perisynaptic and peridendritic astrocyte plasma membrane processes; functional KATP channels confirmed in Bergmann glial cells by slice patch-clamp. Immunocytochemistry with subunit-specific antibodies, ultrastructural immunoelectron microscopy, slice patch-clamp electrophysiology Molecular and cellular neurosciences High 11749042
2004 In primary human coronary artery endothelial cells (HCAEC), KATP channels form a heteromultimeric complex of Kir6.1, Kir6.2, and SUR2B subunits, as demonstrated by reciprocal co-immunoprecipitation and co-localization at the cell surface membrane. Reciprocal co-immunoprecipitation, Western blotting, confocal microscopy immunofluorescence in primary human cells Journal of molecular and cellular cardiology High 15380676
2000 Dominant-negative Kir6.1 suppresses SUR2B+Kir6.1 currents but has no effect on SUR2A+Kir6.2 currents in A549 cells; dominant-negative Kir6.2 has no effect on endogenous KATP current in rabbit ventricular myocytes while dominant-negative Kir6.2 suppresses it, providing functional evidence that Kir6.1 and Kir6.2 do not heteromultimerize and that Kir6.2 is the sole pore-forming subunit of surface KATP channels in cardiac myocytes. Adenoviral dominant-negative gene transfer, whole-cell patch-clamp in A549 cells and rabbit ventricular myocytes The Journal of biological chemistry High 10837494
2006 Knockout of KCNJ8 (Kir6.1) predisposes mice to fatal endotoxic shock by impairing coronary vasodilation in response to cytokine/metabolic signals during LPS-induced sepsis; K+ channel opener treatment improved survival in wild-type but not knockout mice, establishing Kir6.1 as a vascular metabolic sensor for cardiovascular homeostasis in sepsis. Kir6.1 knockout mice, LPS endotoxin model, survival analysis, assessment of cardiac activity and coronary vasodilation, pharmacological rescue with K+ channel opener FASEB journal High 17077304
2010 The KCNJ8-S422L missense mutation causes a gain-of-function in the cardiac Kir6.1 KATP channel with increased current over 0–40 mV range when co-expressed with SUR2A; this gain-of-function is a pathogenic mechanism for J-wave syndromes (Brugada syndrome and early repolarization syndrome). Site-directed mutagenesis, heterologous expression in COS-1 cells with SUR2A, whole-cell patch-clamp Heart rhythm High 20558321
2011 The S422L gain-of-function of Kir6.1/KATP channel is due to reduced sensitivity to intracellular ATP (IC50 785.5 μM for mutant vs. 38.4 μM for WT), resulting in incomplete channel closure under normoxic conditions; the current increase is ~2-fold in whole-cell recordings with SUR2A. Whole-cell and inside-out patch-clamp in TSA201 cells co-expressing KCNJ8 variants with SUR2A, direct sequencing Heart rhythm High 22056721
2014 A de novo Kir6.1[C176S] (p.Cys176Ser) missense mutation causes Cantú syndrome via markedly increased KATP channel activity due to reduced ATP sensitivity, whether co-expressed with SUR1 or SUR2A, establishing KCNJ8 as a causal gene for Cantú syndrome and implicating gain of KATP channel function as the cardinal disease mechanism. Candidate gene screening, heterologous expression of Kir6.1[C176S] with SUR1 or SUR2A, patch-clamp electrophysiology, ATP sensitivity assays Human mutation High 24700710
2002 Protein kinase C (PKC) inhibits Kir6.1/SUR2B channel activity but increases activity of Kir6.2/SUR2B channels; this differential PKC regulation of Kir6.1/SUR2B (but not Kir6.2/SUR2B) mimics native vascular KNDP channels, supporting the composition of vascular KATP channels as Kir6.1/SUR2B homotetramers. Patch-clamp electrophysiology in HEK293 cells expressing Kir6.1/SUR2B, Kir6.2/SUR2B, or combined subunits; purified PKC application; PKC inhibitors; phorbol ester controls The Journal of physiology High 12015420
2007 PKC-dependent inhibition of the Kir6.1/SUR2B channel is mediated by a motif of four serine phosphorylation repeats (Ser-354, Ser-379, Ser-385, Ser-391, Ser-397) in the distal C-terminus of Kir6.1, plus the proximal N-terminus (structural role in gating). Combined mutation of 5 serines to alanine abolished PKC inhibition; in vitro phosphorylation confirmed 4 serines as direct PKC substrates. Kir6.1-Kir6.2 chimeras, site-directed mutagenesis of C-terminal serines, whole-cell patch-clamp in HEK293 cells, in vitro 32P phosphorylation assay with purified PKC The Journal of biological chemistry High 18048350
2007 Arginine vasopressin (AVP) inhibits Kir6.1/SUR2B channel current via the Gq-coupled V1a receptor and PKC pathway, suppressing open-state probability without affecting single-channel conductance; this correlates with AVP-induced vasoconstriction in mesenteric arteries that is reversed by pinacidil. Whole-cell patch-clamp in HEK293 cells co-expressing Kir6.1/SUR2B and V1a receptor; isolated mesenteric artery recordings; PKC inhibitors; phorbol ester controls American journal of physiology. Regulatory, integrative and comparative physiology High 17428891
2008 The intrinsic metabolic sensitivity of Kir6.1/SUR2B channels is not conferred by ATP inhibition of the pore-forming Kir6.1 subunit but rather is a property of the SUR2B regulatory subunit; mutagenesis of key residues in both nucleotide-binding domains (NBDs) of SUR2B implicated both NBDs in governing metabolic sensitivity. 86Rb efflux assays and patch-clamp in HEK293 and CHO cells expressing Kir6.1/SUR2B with NBD mutagenesis Cardiovascular research High 18522960
2011 Loss-of-function KCNJ8 mutations (E332del and V346I) reduce pinacidil-activated KATP current by 40–68% when co-expressed with SUR2A, and were identified in SIDS cases, establishing loss-of-function Kir6.1 mutations as a pathogenic mechanism in SIDS possibly via maladaptive cardiac response to metabolic stress. Comprehensive ORF sequencing of SIDS cohort (292 cases), heterologous expression of mutants with SUR2A in COS-1 cells, whole-cell patch-clamp Circulation. Cardiovascular genetics High 21836131
2013 Smooth muscle-specific gain-of-function expression of ATP-insensitive Kir6.1[G343D] (and Kir6.1[G343D,Q53R]) in mice causes hypotension, reduced vascular contractility, and elevated basal/pinacidil-activated KATP conductance in mesenteric artery myocytes; conversely, loss of Kir6.1 or smooth muscle dominant-negative expression elevates blood pressure, establishing that Kir6.1 overactivity in vascular smooth muscle directly lowers blood pressure. Conditional transgenic mice with tamoxifen-inducible smooth muscle-specific Cre; blood pressure measurement (telemetry and anesthesia); contractility of isolated mesenteric arteries; patch-clamp of isolated myocytes Journal of the American Heart Association High 23974906
2009 LPS upregulates Kir6.1 and SUR2B mRNA and protein in vascular smooth muscle cells via NF-κB-dependent signaling, enhancing KATP channel activity and causing hyperpolarization/vasodilation; Toll-like receptor ligands similarly stimulate Kir6.1/SUR2B expression. Mesenteric arterial ring contractility assays, whole-cell patch-clamp of aortic smooth myocytes, quantitative PCR, NF-κB inhibitors, heterologous expression controls The Journal of biological chemistry High 19959479
1999 Co-expression of Kir6.1 with SUR2B increases the affinity of SUR2B for glibenclamide (KD shifts from ~32 nM for SUR2B alone to ~6 nM for SUR2B/Kir6.1 complex); the K+ channel opener P1075 affinity is unchanged, suggesting Kir6.1 modulates the pharmacology of SUR2B in the assembled channel. Radioligand binding experiments and whole-cell voltage-clamp in intact transfected HEK cells Molecular pharmacology High 10531400
2010 Kir6.1 protein localizes predominantly to the endoplasmic reticulum (ER), not the mitochondria or plasma membrane, in heterologously expressed and endogenous settings; dominant-negative Kir6.1 constructs significantly reduced amplitude and rate of rise of cytosolic Ca2+ transients, implicating Kir6.1 in modulation of ER Ca2+ release. Confocal imaging of Kir6.1-GFP, subcellular fractionation, siRNA knockdown, dominant-negative constructs, Ca2+ imaging in C2C12 muscle cells The Journal of membrane biology Medium 20306027
2017 Kir6.1 contains a 'slide helix' where the V65M (Cantú syndrome) substitution, but not V65L, increases open-state stability and markedly reduces ATP sensitivity and glibenclamide sensitivity in both Kir6.1 and the analogous Kir6.2(V64M), revealing a conserved gating mechanism and predicting that sulfonylurea therapy may be ineffective for this CS mutation class. Ion flux (86Rb efflux) assays and patch-clamp of Kir6.1/Kir6.2 V65M/V65L mutants co-expressed with various SUR subunits in intact cells and excised patches The Journal of biological chemistry High 28842488
2007 Functional Kir6.1/SUR1 channels are located at excitatory presynaptic terminals in hippocampal CA3; genetic deletion of Kir6.1 or SUR1 enhances glutamate release at CA3 synapses and increases seizure susceptibility, establishing Kir6.1/SUR1 as a presynaptic channel that inhibits glutamate release and suppresses epileptiform activity. Immunofluorescence co-localization, whole-cell patch-clamp of glutamate release in knockout mice, seizure susceptibility assays Journal of neurochemistry High 17883401
2014 Kir6.1 physically interacts with Cx43 in cardiomyocyte mitochondria (H9C2 cells) in a phospho-specific manner; hypoxia increases phosphorylation of Cx43 at Ser262 and increases Cx43-Kir6.1 interaction mediated by PKCε; this interaction prevents mitochondria-mediated hypoxia-induced cell apoptosis. Co-immunoprecipitation, co-localization, PKC inhibitor studies, hypoxia model in H9C2 cardiomyocyte cell line Cellular signalling Medium 24815185
2012 Kir6.1 interacts with Cx43 in a phospho-specific manner; Cx43 phosphorylated at Ser262 interacts preferentially with Kir6.1; phospho-deficient S262A mutation abolishes the interaction. Pulldown, co-immunoprecipitation, and co-localization assays; phospho-deficient mutagenesis Experimental cell research Medium 22960107
2019 Kir6.1 physically associates with NLRP3 and inhibits assembly of the NLRP3 inflammasome; Kir6.1 depletion activates NLRP3 inflammasome and worsens insulin resistance in vivo, while Kir6.1 overexpression has opposing effects. Co-immunoprecipitation of endogenous Kir6.1-NLRP3 interaction, KO and overexpression in mice and primary cells, inflammasome activation assays, insulin resistance measurements Experimental & molecular medicine Medium 31387986
2022 Kir6.1 directly interacts with NLRP3 in astrocytes, preventing assembly and activation of the NLRP3 inflammasome; astrocyte-specific Kir6.1 KO promotes astroglial NF-κB activation and extracellular C3 release, which activates neuronal C3aR to induce neuron death in a PD model. Astrocyte-specific Kir6.1 KO mice, LPS-induced PD model, co-immunoprecipitation, NF-κB inhibitor and C3aR antagonist rescue Brain, behavior, and immunity Medium 33838249
2018 Kir6.1 deficiency in microglia enhances M1 polarization and p38 MAPK-NF-κB signaling; Kir6.1 overexpression promotes M2 polarization; in vivo, Kir6.1 deficiency exacerbates dopaminergic neuron death via p38 MAPK-NF-κB, and suppression of p38 MAPK partially rescues the phenotype. Kir6.1 knockdown/overexpression in microglia, KO mouse PD model (MPTP), p38 MAPK inhibitor in vivo rescue, Western blotting for pathway components Cell death & disease Medium 29540778
2019 Astrocytic Kir6.1 KO inhibits mitophagy in astrocytes, resulting in accumulation of damaged mitochondria, increased ROS, and neuroinflammation leading to dopaminergic neuron death; restoration of mitophagy rescues the Kir6.1 KO phenotype. Astrocyte-specific Kir6.1 KO mice, MPTP PD model, in vivo and in vitro mitophagy assays, ROS measurement, mitophagy rescue experiments Brain, behavior, and immunity Medium 31288070
2022 Kir6.1/ABCC9 K-ATP channel cell-autonomously regulates brain vascular smooth muscle cell (VSMC) differentiation by modulating intracellular Ca2+ oscillations via voltage-dependent calcium channels; Kcnj8 KO mice show defective VSMC development, impaired vasoconstrictive capacity, and neuronal-evoked vasodilation leading to local hyperemia. Kcnj8 KO mice, zebrafish chemical/genetic inhibition, cell culture models, Ca2+ imaging, genetic/pharmacological manipulation of K-ATP and voltage-dependent Ca channels Developmental cell High 35588738
2020 Kir6.1 and SUR2B form functional KATP channels in lymphatic smooth muscle (LSM); smooth muscle-specific gain-of-function Kir6.1 expression causes profound lymphatic contractile dysfunction and LSM hyperpolarization partially rescued by glibenclamide; lymphatic endothelium-specific Kir6.1 gain-of-function has no effect on contractile function. PCR subunit identification, pressure myography, global Kir6.1/SUR2 KO mice, smooth muscle-specific and endothelium-specific Kir6.1 GoF transgenic mice, glibenclamide rescue The Journal of physiology High 32372450
2020 Kir6.1/SUR2 subunits underlie KATP channels throughout small intestine and colon smooth muscle; Cantú syndrome knockin mice (KCNJ8 and ABCC9 GoF mutations) exhibit reduced intestinal contractility and GI dysmotility rescued by glibenclamide treatment. Kir6.1/SUR2 KO and human CS mutation knockin mice, intestinal contractility assays, GI transit measurement, glibenclamide treatment JCI insight High 33170808
2016 Gain-of-function Kir6.1[G343D] or [G343D,Q53R] expressed in pancreatic β cells causes glucose intolerance and diabetes via reduced insulin secretion; native Kir6.1 transcripts are expressed in human and mouse islets, indicating Kir6.1 can be incorporated into pancreatic KATP channels and contribute to insulin secretion control. Transgenic mice with β cell-specific (RIP) Kir6.1 GoF expression; BAC transgenic mice; glucose tolerance tests; glucose and sulfonylurea-dependent insulin secretion assays; K+ depolarization controls; qRT-PCR for native Kir6.1 transcripts The Journal of general physiology High 27956473
1999 KATP channels in glucose-receptive neurons of the rat ventromedial hypothalamus are composed of Kir6.1 and SUR1 (not Kir6.2 or SUR2), as shown by single-cell RT-PCR; these channels are activated by glucose removal or metabolic inhibition (65 pS), blocked by sulfonylureas, and also activated by diazoxide and leptin fragment, establishing Kir6.1/SUR1 as the glucose-sensing KATP channel in VMH. Patch-clamp (cell-attached and whole-cell) in brain slices, single-cell RT-PCR from individually harvested neurons The Journal of physiology High 10050011
2020 miR-223, induced by the reactive carbonyl species methylglyoxal (MGO), directly targets the 3'UTR of Kir6.1 mRNA to downregulate its expression; miR-223 overexpression reduces KATP protein, inhibits channel activity, and enhances vasoconstriction; the 3'UTR interaction site was confirmed by mutagenesis luciferase assay. miR-223 overexpression/knockdown in smooth muscle cells, luciferase 3'UTR reporter with mutagenesis, qRT-PCR, Western blot, patch-clamp, perfused mesenteric arterial ring assays Vascular pharmacology High 32151743
2000 Kir6.1 and Kir6.2 are capable of forming heteromeric KATP channels; when co-expressed with SUR2A, co-transfection produces channels with intermediate conductances (between 33.6 pS for Kir6.1/SUR2A and 67.1 pS for Kir6.2/SUR2A); Kir6.1-6.2 tandem protein forms a channel (58.9 pS) with intermediate conductance and lower MgATP sensitivity than Kir6.2. Heterologous co-expression in COS7 cells, single-channel patch-clamp, tandem fusion protein construction Pflugers Archiv : European journal of physiology Medium 11007308
2022 Kir6.1 in astrocytes is an essential negative modulator of NLRP3-mediated pyroptosis; Kir6.1 physically associates with NLRP3 and prevents inflammasome assembly and activation; astrocyte-specific Kir6.1 KO increases NLRP3 inflammasome-mediated astrocytic pyroptosis, inducing depressive-like behaviors in mice. Astrocyte-specific Kir6.1 KO mice, depression models, co-immunoprecipitation of Kir6.1-NLRP3, NLRP3 inflammasome assembly assays, VX-765 (NLRP3 inhibitor) rescue Theranostics Medium 36185602
2024 Kir6.1 (Kcnj8) is required for normal NK cell development; NK cell-specific Kcnj8 ablation results in fewer mature CD27-/CD11b+ and KLRG-1+ NK cells in bone marrow and spleen; patch-clamp confirmed a PNU-37883A-sensitive current in a subset of NK cells. NK cell-specific Kcnj8 KO mice, flow cytometry, patch-clamp electrophysiology, transcriptomics Frontiers in immunology Medium 39687626
1998 CFTR mediates sulphonylurea block of Kir6.1; Kir6.1 expressed alone in NIH3T3 cells is not blocked by glibenclamide, but co-expression with CFTR confers glibenclamide sensitivity (IC50 ~36 μM); CFTR co-expression does not affect Ba2+ block or single-channel conductance of Kir6.1. Heterologous expression in NIH3T3 cells, whole-cell and cell-attached and inside-out patch-clamp The Journal of physiology Medium 9490811
2026 A novel KCNJ8-A88G mutation causes a 2-fold gain-of-function in KATP current with increased single-channel conductance (~73 vs ~46 pS), prolonged open state duration, and drastically reduced ATP sensitivity (IC50 ~1702 vs ~44 μM); molecular dynamics suggest A88G releases restriction of residue F131, causing greater separation of selectivity filter residues and increased conductance. Whole-cell and inside-out patch-clamp in HEK293 cells, single-channel analysis, Kir6.1 homology modelling and molecular dynamics simulations JACC. Clinical electrophysiology High 41995661
2026 Kir6.1-containing KATP channels in ventricular cardiomyocytes are constitutively active and distinct from the canonical Kir6.2/SUR2A channel; cardioprotective stimuli (adenosine, ischaemic preconditioning) increase Kir6.1 channel activity leading to action potential shortening, reduced Ca2+ accumulation, and preserved contractile function; inherent cardioprotection in female cardiomyocytes correlates with increased Kir6.1 activity. Patch-clamp recordings in isolated cardiomyocytes, adenosine and KATP modulator treatment, metabolic inhibition/washout, whole-heart coronary ligation, Ca2+ measurements Frontiers in physiology Medium 42088949

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channel. The Journal of physiology 328 9130167
2002 Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1. Nature medicine 286 11984590
2009 Ventricular fibrillation with prominent early repolarization associated with a rare variant of KCNJ8/KATP channel. Journal of cardiovascular electrophysiology 204 19120683
2010 Gain-of-function mutation S422L in the KCNJ8-encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J-wave syndromes. Heart rhythm 194 20558321
1997 Kir6.1: a possible subunit of ATP-sensitive K+ channels in mitochondria. Biochemical and biophysical research communications 135 9434770
2011 Molecular genetic and functional association of Brugada and early repolarization syndromes with S422L missense mutation in KCNJ8. Heart rhythm 122 22056721
2001 Kir6.1 is the principal pore-forming subunit of astrocyte but not neuronal plasma membrane K-ATP channels. Molecular and cellular neurosciences 106 11749042
2005 Pore-forming subunits of K-ATP channels, Kir6.1 and Kir6.2, display prominent differences in regional and cellular distribution in the rat brain. The Journal of comparative neurology 104 15739238
2012 A KCNJ8 mutation associated with early repolarization and atrial fibrillation. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 95 22562657
2014 Cantú syndrome resulting from activating mutation in the KCNJ8 gene. Human mutation 94 24700710
2013 Mutation of KCNJ8 in a patient with Cantú syndrome with unique vascular abnormalities - support for the role of K(ATP) channels in this condition. European journal of medical genetics 84 24176758
1999 Glucose-receptive neurones in the rat ventromedial hypothalamus express KATP channels composed of Kir6.1 and SUR1 subunits. The Journal of physiology 82 10050011
2004 K ATP channels of primary human coronary artery endothelial cells consist of a heteromultimeric complex of Kir6.1, Kir6.2, and SUR2B subunits. Journal of molecular and cellular cardiology 78 15380676
2018 Kir6.1/K-ATP channel modulates microglia phenotypes: implication in Parkinson's disease. Cell death & disease 70 29540778
2006 Gene knockout of the KCNJ8-encoded Kir6.1 K(ATP) channel imparts fatal susceptibility to endotoxemia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 69 17077304
1996 The sulphonylurea receptor confers diazoxide sensitivity on the inwardly rectifying K+ channel Kir6.1 expressed in human embryonic kidney cells. The Journal of physiology 68 8865068
2019 Kir6.1/K-ATP channel on astrocytes protects against dopaminergic neurodegeneration in the MPTP mouse model of Parkinson's disease via promoting mitophagy. Brain, behavior, and immunity 65 31288070
2013 Hypotension due to Kir6.1 gain-of-function in vascular smooth muscle. Journal of the American Heart Association 61 23974906
1995 cDNA sequence, gene structure, and chromosomal localization of the human ATP-sensitive potassium channel, uKATP-1, gene (KCNJ8). Genomics 60 8595887
2014 Protein kinase C (PKC) mediated interaction between conexin43 (Cx43) and K(+)(ATP) channel subunit (Kir6.1) in cardiomyocyte mitochondria: Implications in cytoprotection against hypoxia induced cell apoptosis. Cellular signalling 56 24815185
2007 Is Kir6.1 a subunit of mitoK(ATP)? Biochemical and biophysical research communications 56 18068667
2003 Differential expression of Kir6.1 and SUR2B mRNAs in the vasculature of various tissues in rats. The Journal of membrane biology 52 14724757
2020 Kir6.1-dependent KATP channels in lymphatic smooth muscle and vessel dysfunction in mice with Kir6.1 gain-of-function. The Journal of physiology 51 32372450
2002 Protein kinase C modulation of recombinant ATP-sensitive K(+) channels composed of Kir6.1 and/or Kir6.2 expressed with SUR2B. The Journal of physiology 49 12015420
2011 Loss-of-function mutations in the KCNJ8-encoded Kir6.1 K(ATP) channel and sudden infant death syndrome. Circulation. Cardiovascular genetics 48 21836131
1999 Coexpression with the inward rectifier K(+) channel Kir6.1 increases the affinity of the vascular sulfonylurea receptor SUR2B for glibenclamide. Molecular pharmacology 44 10531400
2000 Evidence against functional heteromultimerization of the KATP channel subunits Kir6.1 and Kir6.2. The Journal of biological chemistry 43 10837494
2022 KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling. Developmental cell 41 35588738
2009 Lipopolysaccharides up-regulate Kir6.1/SUR2B channel expression and enhance vascular KATP channel activity via NF-kappaB-dependent signaling. The Journal of biological chemistry 41 19959479
2000 The properties of the Kir6.1-6.2 tandem channel co-expressed with SUR2A. Pflugers Archiv : European journal of physiology 41 11007308
2007 Expression of functional Kir6.1 channels regulates glutamate release at CA3 synapses in generation of epileptic form of seizures. Journal of neurochemistry 38 17883401
2016 Propofol Suppressed Hypoxia/Reoxygenation-Induced Apoptosis in HBVSMC by Regulation of the Expression of Bcl-2, Bax, Caspase3, Kir6.1, and p-JNK. Oxidative medicine and cellular longevity 34 27057270
2021 Astrocytic Kir6.1 deletion aggravates neurodegeneration in the lipopolysaccharide-induced mouse model of Parkinson's disease via astrocyte-neuron cross talk through complement C3-C3R signaling. Brain, behavior, and immunity 33 33838249
1998 Cystic fibrosis transmembrane conductance regulator mediates sulphonylurea block of the inwardly rectifying K+ channel Kir6.1. The Journal of physiology 33 9490811
2022 Kir6.1/K-ATP channel in astrocytes is an essential negative modulator of astrocytic pyroptosis in mouse model of depression. Theranostics 31 36185602
2013 The antiepileptic effect of the glycolytic inhibitor 2-deoxy-D-glucose is mediated by upregulation of K(ATP) channel subunits Kir6.1 and Kir6.2. Neurochemical research 31 23475455
2002 ATP-sensitive K(+) channels composed of Kir6.1 and SUR2B subunits in guinea pig gastric myocytes. American journal of physiology. Gastrointestinal and liver physiology 31 11751167
2017 Conserved functional consequences of disease-associated mutations in the slide helix of Kir6.1 and Kir6.2 subunits of the ATP-sensitive potassium channel. The Journal of biological chemistry 30 28842488
2013 Kir6.1 knockdown aggravates cerebral ischemia/reperfusion-induced neural injury in mice. CNS neuroscience & therapeutics 30 23663330
2007 A short motif in Kir6.1 consisting of four phosphorylation repeats underlies the vascular KATP channel inhibition by protein kinase C. The Journal of biological chemistry 28 18048350
2007 Arginine vasopressin inhibits Kir6.1/SUR2B channel and constricts the mesenteric artery via V1a receptor and protein kinase C. American journal of physiology. Regulatory, integrative and comparative physiology 27 17428891
2004 Pore loop-mutated rat KIR6.1 and KIR6.2 suppress KATP current in rat cardiomyocytes. American journal of physiology. Heart and circulatory physiology 27 15044189
2004 Selective expression of Kir6.1 protein in different vascular and non-vascular tissues. Biochemical pharmacology 26 14667937
2020 Kir6.1- and SUR2-dependent KATP overactivity disrupts intestinal motility in murine models of Cantú syndrome. JCI insight 25 33170808
2018 Astrocyte-specific deletion of Kir6.1/K-ATP channel aggravates cerebral ischemia/reperfusion injury through endoplasmic reticulum stress in mice. Experimental neurology 25 30315808
2002 Cloning of rabbit Kir6.1, SUR2A, and SUR2B: possible candidates for a renal K(ATP) channel. American journal of physiology. Renal physiology 25 11788443
1999 Block of human aorta Kir6.1 by the vascular KATP channel inhibitor U37883A. British journal of pharmacology 25 10516647
1997 Channel activators regulate ATP-sensitive potassium channel (KIR6.1) expression in chick cardiomyocytes. FEBS letters 23 9257703
2008 Decreased expression of aortic KIR6.1 and SUR2B in hypertension does not correlate with changes in the functional role of K(ATP) channels. European journal of pharmacology 21 18471810
2008 Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits. Cardiovascular research 21 18522960
2012 Adenosine-triphosphate-sensitive K+ channel (Kir6.1): a novel phosphospecific interaction partner of connexin 43 (Cx43). Experimental cell research 20 22960107
2003 The Kir6.1-protein, a pore-forming subunit of ATP-sensitive potassium channels, is prominently expressed by giant cholinergic interneurons in the striatum of the rat brain. Brain research 20 12965237
2002 SURI and Kir6.1 subunits of K(ATP)-channels are co-localized in retinal glial (Müller) cells. Neuroreport 20 11924895
1998 Genomic organization and expression of KCNJ8/Kir6.1, a gene encoding a subunit of an ATP-sensitive potassium channel. Gene 20 9573340
2010 The intracellular localization and function of the ATP-sensitive K+ channel subunit Kir6.1. The Journal of membrane biology 19 20306027
2019 The pore-forming subunit Kir6.1 of the K-ATP channel negatively regulates the NLRP3 inflammasome to control insulin resistance by interacting with NLRP3. Experimental & molecular medicine 18 31387986
2008 ATP-sensitive K+ channels in pig urethral smooth muscle cells are heteromultimers of Kir6.1 and Kir6.2. American journal of physiology. Renal physiology 18 18945825
2007 Expression of ATP sensitive K+ channel subunit Kir6.1 in rat kidney. European journal of histochemistry : EJH 18 17548268
2010 Activation of SUR2B/Kir6.1 subtype of adenosine triphosphate-sensitive potassium channel improves pressure overload-induced cardiac remodeling via protecting endothelial function. Journal of cardiovascular pharmacology 17 20505525
2014 Total flavonoids from Ganshanbian (Herba Hyperici Attenuati) effect the expression of CaL-alpha1C and K(ATP)-Kir6.1 mRNA of the myocardial cell membrane in myocardial ischemia-reperfusion arrhythmia rats. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan 16 24992765
2013 The KCNJ8-S422L variant previously associated with J-wave syndromes is found at an increased frequency in Ashkenazi Jews. European journal of human genetics : EJHG 14 23632791
2003 Iptkalim inhibits cocaine challenge-induced enhancement of dopamine levels in nucleus accumbens and striatum of rats by up-regulating Kir6.1 and Kir6.2 mRNA expression. Acta pharmacologica Sinica 14 12791178
2021 Zoledronic Acid as a Novel Dual Blocker of KIR6.1/2-SUR2 Subunits of ATP-Sensitive K+ Channels: Role in the Adverse Drug Reactions. Pharmaceutics 13 34575427
2009 Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1. The Journal of biological chemistry 13 19139106
2021 KATP Opener Attenuates Diabetic-Induced Müller Gliosis and Inflammation by Modulating Kir6.1 in Microglia. Investigative ophthalmology & visual science 12 33523201
2018 From in silico to in vitro: a trip to reveal flavonoid binding on the Rattus norvegicus Kir6.1 ATP-sensitive inward rectifier potassium channel. PeerJ 12 29736333
2018 SUR2B/Kir6.1 channel openers correct endothelial dysfunction in chronic heart failure via the miR-1-3p/ET-1 pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 12 30530045
2020 Memantine Improves Depressive-like Behaviors via Kir6.1 Channel Inhibition in Olfactory Bulbectomized Mice. Neuroscience 11 32531473
2005 Mediation of the effect of nicotine on Kir6.1 channels by superoxide anion production. Journal of cardiovascular pharmacology 11 15821440
2016 Diabetes induced by gain-of-function mutations in the Kir6.1 subunit of the KATP channel. The Journal of general physiology 10 27956473
2021 Kir6.1 improves cardiac dysfunction in diabetic cardiomyopathy via the AKT-FoxO1 signalling pathway. Journal of cellular and molecular medicine 9 33547878
2009 Genes controlling postural changes in blood pressure: comprehensive association analysis of ATP-sensitive potassium channel genes KCNJ8 and ABCC9. Physiological genomics 9 19952277
2003 Absence of Kir6.1/KCNJ8 mutations in Italian patients with abnormal coronary vasomotion. International journal of molecular medicine 9 12964027
2023 Involvement of SUR2/Kir6.1 channel in the physiopathology of pulmonary arterial hypertension. Frontiers in cardiovascular medicine 8 36704469
2022 Cantù syndrome: Report of a patient with a novel variant in KCNJ8 and revision of literature. American journal of medical genetics. Part A 7 35243770
2012 Association of muscarinic M₃ receptors and Kir6.1 with caveolae in human detrusor muscle. European journal of pharmacology 7 22410194
2017 Electrophysiological analyses of transgenic mice overexpressing KCNJ8 with S422L mutation in cardiomyocytes. Journal of pharmacological sciences 6 28928055
2016 Pharmacological evidence: a new therapeutic approach to the treatment of chronic heart failure through SUR2B/Kir6.1 channel in endothelial cells. Acta pharmacologica Sinica 6 27890915
2015 Diazoxide Cardioprotection Is Independent of Adenosine Triphosphate-Sensitive Potassium Channel Kir6.1 Subunit in Response to Stress. Journal of the American College of Surgeons 6 25872691
2013 Oleic acid inhibits the K(ATP) channel subunit Kir6.1 and the K(ATP) current in human umbilical artery smooth muscle cells. The American journal of the medical sciences 6 23114200
2006 Mutational analysis of Kir6.1 in Japanese patients with coronary spastic angina. International journal of molecular medicine 6 16964409
2017 MiR-20 regulates myocardiac ischemia by targeting KATP subunit Kir6.1. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 5 28786072
2023 Zoledronic Acid Blocks Overactive Kir6.1/SUR2-Dependent KATP Channels in Skeletal Muscle and Osteoblasts in a Murine Model of Cantú Syndrome. Cells 4 36980269
2016 Increased tolerance to stress in cardiac expressed gain-of-function of adenosine triphosphate-sensitive potassium channel subunit Kir6.1. The Journal of surgical research 4 27884343
2010 [Effects of Guanxinkang on expressions of ATP-sensitive potassium channel subunits Kir6.1, Kir6.2, SUR2A and SUR2B in ischemic myocytes of rats]. Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine 4 20456845
2020 Methylglyoxal-induced miR-223 suppresses rat vascular KATP channel activity by downregulating Kir6.1 mRNA in carbonyl stress. Vascular pharmacology 3 32151743
2019 Kir6.1 Heterozygous Mice Exhibit Aberrant Amygdala-Dependent Cued Fear Memory. Molecular neurobiology 3 31808063
2011 Mutational analysis of the Kir6.1 gene in Chinese hypertensive patients treated with the novel ATP-sensitive potassium channel opener iptakalim. Experimental and therapeutic medicine 3 22977571
2018 Ectopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy. Scientific reports 2 30082733
2016 ATP-sensitive K(+) channels (Kir6.1/SUR1) regulate gap junctional coupling in cochlear-supporting cells. Pflugers Archiv : European journal of physiology 2 27030354
2025 Automated patch clamp analysis of heterologously expressed Kir6.2/SUR1 and Kir6.1/SUR2B KATP currents. American journal of physiology. Cell physiology 1 40465479
2024 Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development. bioRxiv : the preprint server for biology 1 39211194
2018 ATP sensitive K+ channel subunits (Kir6.1, Kir6.2) are the candidate mediators regulating ameliorating effects of pulsed magnetic field on aortic contractility in diabetic rats. Bioelectromagnetics 1 29446477
2017 Effects of corticotropin-releasing hormone on the expression of adenosine triphosphate-sensitive potassium channels (Kir6.1/SUR2B) in human term pregnant myometrium. Obstetrics & gynecology science 1 29372145
2012 [Protective effects of SUR2B/Kir6.1 potassium channel opener natakalim against RAVECs injuries induced by hypoxia]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 1 22860425
2026 Biophysical Characterization of a Novel KCNJ8 Rare Variant Linked With Inherited and Acquired J Wave Syndrome. JACC. Clinical electrophysiology 0 41995661
2026 Cardiac ventricular Kir6.1 ATP-sensitive potassium channels: an overlooked effector of cardioprotection. Frontiers in physiology 0 42088949
2024 Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development. Frontiers in immunology 0 39687626
2022 [Interventional effects of activating SUR2B/Kir6.1-type KATP channels on renal cells injury and its mechanisms]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 0 37308403
2020 BPI and KIR6.1 as significant hub genes for vein graft restenosis. The Journal of international medical research 0 33259239

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