Affinage

KCNJ6

G protein-activated inward rectifier potassium channel 2 · UniProt P48051

Length
423 aa
Mass
48.5 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 37 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

KCNJ6 encodes GIRK2 (Kir3.2), the principal neuronal subunit of G-protein-gated inwardly rectifying K+ channels that couple inhibitory GPCRs to membrane hyperpolarization and thereby set neuronal excitability across multiple circuits (PMID:9342388, PMID:12040038). GIRK2 assembles into functional tetramers as homomers in dopaminergic substantia nigra neurons and as heteromers with GIRK1 or GIRK3 in cortex, hippocampus, and cerebellum, where loss of GIRK2 destabilizes the partner subunit (PMID:8929423, PMID:9342388, PMID:9920664, PMID:10956667). Channel opening requires the simultaneous, obligatory presence of both Gβγ and PIP2: reconstitution of purified GIRK2 in lipid bilayers showed neither ligand alone activates the channel, and Gαi(GDP) closes it by sequestering Gβγ (PMID:25049222). Crystal and Gβγ-complex structures defined two sequential gates — a cytoplasmic G-loop gate and a transmembrane inner-helix gate — with four Gβγ subunits binding cooperatively at subunit interfaces to drive a pre-open state, and an intracellular Na+ site that amplifies Gβγ affinity to provide activity-dependent feedback inhibition (PMID:21962516, PMID:23739333, PMID:27074662). Cholesterol/CHS binds adjacent to the PIP2 site and stabilizes channel opening, while PIP2 itself binds cooperatively with isoform-selective residues controlling lipid specificity (PMID:34433062, PMID:32372643). Through these inputs GIRK2 serves as the postsynaptic effector for GABAB, opioid, α2-adrenergic, muscarinic, cannabinoid, adenosine, and 5-HT1A receptors, mediating analgesia, neuronal excitability control, cardiac rate modulation, mood regulation, and energy homeostasis (PMID:12496346, PMID:12493843, PMID:12040038, PMID:18303085, PMID:25956878, PMID:37594983). De novo pore-region mutations in KCNJ6 cause Keppen-Lubinsky syndrome, and a gain-of-function pore mutation produces an aberrant, non-selective basal current mirroring the classic weaver phenotype (PMID:25620207, PMID:29852244, PMID:8630252).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1996 High

    Established that GIRK2 is a physiological channel subunit that physically assembles with GIRK1 in vivo and whose pore mutation underlies a neurodevelopmental disease, answering what GIRK2 partners with and how its dysfunction causes pathology.

    Evidence Reciprocal co-IP from rat/mouse brain and Xenopus oocyte electrophysiology of the weaver G156S pore mutant with pharmacological rescue of granule cells

    PMID:8630252 PMID:8706831 PMID:8929423

    Open questions at the time
    • Stoichiometry of native heteromers not resolved
    • Mechanism by which GIRK2 stabilizes GIRK1 protein levels unknown
  2. 1996 Medium

    Defined GIRK2 splice variants and showed GIRK2B forms functional G-protein-gated channels with GIRK1, addressing isoform diversity at the channel level.

    Evidence cDNA cloning and Xenopus oocyte co-expression with GIRK1 and m2 receptor

    PMID:8573147

    Open questions at the time
    • In vivo role of GIRK2B not established
    • Single-lab functional characterization
  3. 1997 High

    Demonstrated genetically that GIRK2 is the obligatory effector for GABAB receptor-activated K+ currents and is required for normal neuronal excitability, linking the channel to inhibitory neurotransmission and seizure susceptibility.

    Evidence Girk2 knockout mouse electrophysiology in cerebellar granule cells and behavioral seizure testing

    PMID:9023358 PMID:9342388

    Open questions at the time
    • Does not dissect contributions of individual heteromeric partners
    • Circuit-level basis of seizures not mapped
  4. 1999 Medium

    Resolved the molecular subunit composition and postsynaptic targeting of native GIRK2 channels, showing homomeric Kir3.2 in substantia nigra and PSD-95 binding by the Kir3.2c splice variant for dendritic localization.

    Evidence IP/Western, immunohistochemistry, and heterologous electrophysiology of Kir3.2a/c splice variants; co-IP with PSD-95

    PMID:9920664

    Open questions at the time
    • Single-lab co-IP for PSD-95 interaction
    • Functional consequence of acrosomal localization unexplored
  5. 1999 Medium

    Used engineered subunit arrangements to explain selective neuronal vulnerability, showing GIRK1 rescues the weaver pore defect in a position-dependent manner.

    Evidence Xenopus oocyte expression of tandem dimers and linked tetramers

    PMID:10493734

    Open questions at the time
    • Native subunit arrangement not directly observed
    • Single-lab reconstitution
  6. 2000 Medium

    Showed GIRK2/GIRK3 heteromers form in brain and that RGS proteins gate the kinetics and duration of GIRK1/GIRK2 activation, extending the channel's regulatory and partner repertoire.

    Evidence Co-IP from transfected cells and native brain plus CHO patch-clamp; Xenopus oocyte voltage-clamp with RGS4 and kappa-opioid receptor

    PMID:10956667 PMID:11065178

    Open questions at the time
    • RGS4 evidence from single heterologous study
    • Physiological role of GIRK2/GIRK3 heteromers in vivo unclear
  7. 2002 High

    Established GIRK2 as the dominant postsynaptic effector mediating analgesia from multiple GPCRs and acute opioid hyperpolarization, defining its in vivo pharmacological coupling.

    Evidence Girk2 (and Kir3.3) knockout mice in nociceptive behavioral assays and locus coeruleus slice electrophysiology with multiple agonists

    PMID:12040038 PMID:12493843 PMID:12496346

    Open questions at the time
    • Relative contribution of each receptor to specific circuits not fully resolved
    • Sex-difference mechanism not defined
  8. 2003 High

    Mapped the Gβγ-binding determinants in GIRK2 N- and C-termini and distinguished binding from gating residues, clarifying the molecular basis of G-protein activation.

    Evidence Pull-down binding assays with subunit fragments, Gαi1 competition, and mutagenesis with Xenopus oocyte electrophysiology

    PMID:12743112

    Open questions at the time
    • Structural basis of binding-vs-gating distinction not resolved in this work
    • Single-lab study
  9. 2004 High

    Demonstrated spinal GIRK1/GIRK2 channels mediate thermal nociception and high-dose morphine analgesia, with reciprocal subunit dependence confirming physical interaction.

    Evidence GIRK1 and GIRK2 knockout mice in tail-flick assays with intrathecal drug delivery, Western blot, and tertiapin pharmacology

    PMID:15028774

    Open questions at the time
    • Cellular site of spinal GIRK action not pinpointed
  10. 2006 High

    Revealed compartment-specific subcellular targeting, with spine Kir3.2 co-clustering with GABAB receptors while shaft channels segregate, suggesting input-specific signaling.

    Evidence Quantitative immunogold and SDS-FRL in hippocampal pyramidal cells

    PMID:16624949

    Open questions at the time
    • Functional consequence of compartmentalization not directly tested electrophysiologically
    • Single-lab analysis
  11. 2008 Medium

    Showed KCNJ6 overexpression alters cardiac rate control at the sino-atrial node, extending GIRK2 function beyond the CNS.

    Evidence Transgenic human-KCNJ6 mice with ECG and muscarinic/adenosinergic pharmacological challenge

    PMID:18303085

    Open questions at the time
    • Endogenous cardiac GIRK2 contribution not assessed by loss-of-function
    • Single-lab study
  12. 2009 High

    Identified GIRK1-specific regulation by Gαi3-GDP, distinguishing heteromer-specific tuning from GIRK2-intrinsic gating.

    Evidence Xenopus oocyte electrophysiology with Gα mutants, in vitro pull-down, and GIRK1/GIRK2 chimeras

    PMID:19470775

    Open questions at the time
    • Does not address GIRK2-homomer regulation, which is insensitive
  13. 2011 High

    Provided the first structural framework for gating, defining two gates and a Na+ site and showing PIP2 couples the G-loop and inner-helix gates.

    Evidence X-ray crystallography of wild-type and constitutively active GIRK2 with and without PIP2

    PMID:21962516

    Open questions at the time
    • Gβγ engagement not yet visualized structurally at this stage
  14. 2012 Medium

    Captured dynamic conformational rearrangements at the Gβγ/Kir3 interface upon receptor activation in a pre-formed signaling complex, linking ligand efficacy to channel gating.

    Evidence BRET, co-IP, pertussis toxin, and mutagenesis in HEK293 cells (Kir3.1/Kir3.2 heteromer)

    PMID:23175530

    Open questions at the time
    • Performed on GIRK1-containing heteromers
    • Single-lab live-cell biosensor data
  15. 2013 High

    Solved the GIRK2–Gβγ complex structure, showing four Gβγ binding cooperatively at subunit interfaces to induce a pre-open intermediate, and established GIRK2 sufficiency for peripheral opioid analgesia.

    Evidence 3.5 Å crystallography of the GIRK2–Gβγ complex; transgenic GIRK expression in mouse nociceptors with behavioral assays and cross-species immunohistochemistry

    PMID:23739333 PMID:23818182

    Open questions at the time
    • Full open-state transition from pre-open not captured
    • Determinants of species-specific sensory expression only partially mapped
  16. 2014 High

    Reconstituted the obligatory dual Gβγ+PIP2 activation requirement with purified components and identified a trafficking-based pharmacological activation mechanism.

    Evidence Planar lipid bilayer reconstitution of purified GIRK2 with patch-clamp; tethered protein scaffold selection of activator N5

    PMID:25028803 PMID:25049222

    Open questions at the time
    • N5 mechanism described only at the level of internalization
    • Cooperativity origin (Hill ~2.5) not structurally explained
  17. 2015 Medium

    Established KCNJ6 as a Mendelian disease gene, linking pore-region de novo mutations to Keppen-Lubinsky syndrome.

    Evidence Whole-exome sequencing of three unrelated patients with genotype-phenotype correlation to animal models

    PMID:25620207

    Open questions at the time
    • No direct functional assay of patient mutations in this study
    • Loss- vs gain-of-function consequence not biophysically tested here
  18. 2016 High

    Quantified the cooperative dual-input mechanism, showing Na+ amplifies channel opening by increasing Gβγ affinity to provide activity-dependent feedback, and linked GIRK2 to serotonergic autoinhibition.

    Evidence Membrane-anchored Gβγ concentration assays with dopamine-neuron electrophysiology; dorsal raphe in vivo recordings in Girk2 KO with tertiapin-Q and behavior

    PMID:25956878 PMID:27074662

    Open questions at the time
    • Native concentrations of Gβγ/Na+ during physiological firing not directly measured
    • Antidepressant-resistance mechanism only correlative
  19. 2017 High

    Defined isoform-specific subcellular distribution and behavioral roles, and demonstrated Kcnj6 gene dosage drives Down-syndrome synaptic and cognitive dysfunction.

    Evidence Viral isoform expression in Girk2-null hippocampal neurons with electrophysiology and fear conditioning; genetic copy-number reduction in Ts65Dn mice with LTP and memory assays plus fluoxetine pharmacology

    PMID:28342823 PMID:28487514

    Open questions at the time
    • Molecular basis of isoform distribution differences incompletely defined
  20. 2018 High

    Showed a de novo pore mutation produces a weaver-like gain-of-function with loss of K+ selectivity and gained Ca2+ permeability, defining a pathogenic mechanism distinct from simple loss of function.

    Evidence Whole-exome sequencing and heterologous expression of the L171R mutant with patch-clamp and QX-314 pharmacology

    PMID:29852244

    Open questions at the time
    • In vivo phenotype of L171R not modeled
    • Heterotetramer non-functionality inferred from tandem dimer only
  21. 2020 Medium

    Resolved PIP2 cooperativity and isoform selectivity at the residue level, refining how lipid identity tunes GIRK2 activation.

    Evidence Native mass spectrometry and fluorescent lipid binding assays with site-directed mutagenesis

    PMID:32372643

    Open questions at the time
    • Physiological relevance of altered PIP isoform selectivity not tested in cells
    • Single-lab biophysical data
  22. 2021 High

    Identified cholesterol as a structural modulator binding near PIP2 to stabilize the open state, integrating lipid environment into the gating model.

    Evidence Cryo-EM of GIRK2 ± CHS ± PIP2 with mutagenesis of the CHS pocket and functional validation

    PMID:34433062

    Open questions at the time
    • Native cholesterol regulation in neurons not directly demonstrated
  23. 2023 High

    Defined a cell-type-specific role in energy homeostasis, showing GIRK2 stabilizes AgRP neuron excitability to control sympathetic tone and energy expenditure.

    Evidence AgRP-selective conditional Girk2 knockout with electrophysiology, metabolic phenotyping, and sympathetic activity measurement

    PMID:37594983

    Open questions at the time
    • Upstream GPCR driving AgRP GIRK2 signaling not identified
  24. 2023 Medium

    Linked KCNJ6 regulatory variants to alcohol-use phenotypes via GIRK2 expression-dependent control of human neuronal excitability.

    Evidence iPSC-derived glutamatergic neurons from AUD patients with single-cell RNA-seq, patch-clamp, morphology, and GIRK2 overexpression rescue

    PMID:36207584

    Open questions at the time
    • Causal noncoding variant mechanism not fully defined
    • In vivo relevance to AUD not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the sequential gates, multi-ligand cooperativity, and isoform/partner-specific tuning are integrated dynamically in native circuits to produce precise context-dependent inhibition remains unresolved.
  • No native-membrane structure of a fully open GPCR–Gβγ–GIRK2 signaling complex
  • Quantitative in vivo dynamics of Na+/Gβγ/PIP2 co-regulation during firing unmeasured
  • Direct functional assays of most disease mutations lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0005198 structural molecule activity 4 GO:0008289 lipid binding 3 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-1430728 Metabolism 1
Partners
DLG4GABBR1GNAI3GNB1GNG2KCNJ3KCNJ9RGS4
Complex memberships
GIRK1/GIRK2 heterotetramerGIRK2 homotetramerGIRK2/GIRK3 heterotetramerGPCR-Gβγ-GIRK2 signaling complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 Crystal structure of mammalian GIRK2 (homotetrameric) revealed a G-loop gate in the cytoplasmic domain and an inner helix gate in the transmembrane domain. Comparison of wild-type and constitutively active mutant structures showed that G proteins open only the G-loop gate in the absence of PIP2, but in the presence of PIP2 the G-loop and inner helix gates become coupled so both open simultaneously. An intracellular Na+ ion-binding site was also identified, providing a structural basis for Na+-dependent modulation of channel activity. X-ray crystallography of wild-type and constitutively active mutant GIRK2 in the absence and presence of PIP2 Cell High 21962516
2013 3.5 Å crystal structure of mammalian GIRK2 in complex with βγ G-protein subunits revealed that four Gβγ subunits bind at interfaces between four K+ channel subunits via short-range atomic and long-range electrostatic interactions, inducing a pre-open state intermediate between closed and fully open conformations. This structure is compatible with membrane-delimited activation and burst kinetics, and shows how PIP2 and Na+ participate in multi-ligand regulation. X-ray crystallography of GIRK2–Gβγ complex at 3.5 Å resolution Nature High 23739333
2014 Purified mammalian GIRK2 reconstituted in planar lipid bilayers showed that Gβγ and PIP2 must both be present simultaneously to activate the channel. Gαi1(GTPγS) has no activating effect, while Gαi1(GDP) closes the channel by removing Gβγ. Na+ is not essential but modulates Gβγ/PIP2 effects over physiological concentrations. GIRK2 opens as a function of PIP2 mole fraction with Hill coefficient ~2.5. Reconstitution of purified GIRK2 in planar lipid membranes; patch-clamp electrophysiology with defined purified protein components eLife High 25049222
2016 Using membrane-anchored G protein concentration assays, four Gβγ subunits were shown to bind cooperatively to open GIRK2 (neuronal homomeric channel). Intracellular Na+, which enters neurons during action potentials, amplifies channel opening primarily by increasing Gβγ binding affinity, establishing a dual-input activation mechanism that provides activity-dependent feedback inhibition. Functional assay of GIRK2 activity vs. membrane-anchored Gβγ concentration in cell-based system; electrophysiology in mouse dopamine neurons eLife High 27074662
2021 Cryo-EM structures of GIRK2 in the presence and absence of cholesterol analog CHS and PIP2 revealed that CHS binds in lipid-facing hydrophobic pockets of the transmembrane domain near the PIP2 binding site. CHS stabilizes PIP2 interaction with the channel and promotes engagement of the cytoplasmic domain onto the transmembrane region. Mutagenesis of one CHS-binding pocket eliminated cholesterol-dependent potentiation. Cryo-electron microscopy structures of GIRK2 ± CHS ± PIP2; mutagenesis of CHS-binding site with functional assay Cell reports High 34433062
1996 GIRK2 and GIRK1 co-immunoprecipitate from brain regions where both are expressed (cerebral cortex, hippocampus, cerebellum), demonstrating that they form heteromeric channels in vivo. In weaver mouse brain, GIRK2 expression is dramatically decreased and GIRK1 expression is also disrupted in regions of co-assembly. Co-immunoprecipitation from rat and mouse brain tissue; immunohistochemistry The Journal of neuroscience Medium 8929423
1996 The weaver mutation (G156S in the H5/pore region of GIRK2) causes constitutive activation, loss of K+ selectivity (increased Na+ permeability), and increased sensitivity to channel blockers when expressed in Xenopus oocytes. Pharmacological blockade of Na+ influx in weaver granule cells rescues their ability to differentiate, establishing that Na+ flux through mutant GIRK2 underlies granule cell development failure. Xenopus oocyte expression of weaver GIRK2; electrophysiology; pharmacological rescue of weaver cerebellar granule cells in culture Neuron High 8630252
1996 The weaver G156S mutation in the pore region of GIRK2 causes loss of high K+ selectivity over Na+, resulting in increased basal Na+ permeability and membrane depolarization in Xenopus oocytes. This loss of selectivity persists when weaver GIRK2 is coexpressed with GIRK1. Xenopus oocyte expression; electrophysiology/ion substitution experiments FEBS letters High 8706831
1997 GIRK2 knockout mice lack GABAB receptor-activated inwardly rectifying K+ currents in cerebellar granule cells, and GIRK1 expression is reduced in regions normally co-expressing both subunits. This establishes that GABAB receptors couple to heteromultimers of GIRK1 and GIRK2, and that GIRK2 is required for maintaining GIRK1 protein levels in these complexes. Electrophysiology of cerebellar granule cells from Girk2 null and weaver mice; Western blot for GIRK1 expression Proceedings of the National Academy of Sciences of the United States of America High 9342388
1999 In the substantia nigra, GIRK channels are composed only of Kir3.2 (GIRK2) subunits (homotetramers of Kir3.2a and Kir3.2c splice variants), without significant Kir3.1 or Kir3.3 content, and are localized specifically at postsynaptic membranes on dopaminergic neuron dendrites. Kir3.2c, but not Kir3.2a, binds PDZ domain-containing protein PSD-95. Kir3.2a alone or Kir3.2a+Kir3.2c were activated by G-protein stimulation, but Kir3.2c alone was not. Immunoprecipitation, Western blot, immunohistochemistry, heterologous expression electrophysiology in Xenopus oocytes The Journal of neuroscience High 9920664
2000 GIRK2 and GIRK3 co-assemble to form functional heteromultimeric K+ channels in brain. Co-expressed GIRK2/GIRK3 channels showed ~5-fold lower sensitivity to activation by Gβγ compared to GIRK1/GIRKx channels. Complexes containing only GIRK2 and GIRK3 were immunoprecipitated from transfected cells and purified from native brain tissue. Co-transfection in CHO-K1 cells; patch-clamp electrophysiology; co-immunoprecipitation from transfected cells and native brain The Journal of biological chemistry High 10956667
2003 Gβγ binds to both the N-terminus and a segment of the C-terminus (~residues 320–409 by GIRK1 count, corresponding residues in GIRK2) of GIRK2. The Gβγ-binding sites in GIRK1 and GIRK2 C-termini are not identical; GIRK1 has an additional binding segment in the first half of its C-terminus that GIRK2 lacks. Key leucine residues (L273, L344 in GIRK2) are important for Gβγ-induced gating changes rather than Gβγ binding per se. Pull-down binding assays with GIRK subunit fragments; competition assays with Gαi1; mutagenesis with functional electrophysiology in Xenopus oocytes The Journal of biological chemistry High 12743112
2009 The GDP-bound form of Gαi3 (inactive state) regulates GIRK1-containing heteromeric channels by forming heterotrimers and reducing basal activity while increasing Gβγ-evoked current. This Gαi3-GDP regulation is unique to GIRK1 subunit-containing channels; homomeric GIRK2 channels are insensitive to Gαi3GDP. In vitro binding showed Gβγ enhances binding of Gαi3GDP to the cytosolic domain of GIRK1 but not GIRK2. The distal C-terminus of GIRK1 confers this differential regulation. Electrophysiology in Xenopus oocytes with coexpression of constitutively inactive/active Gα mutants; in vitro pull-down protein interaction assays; chimeric GIRK1/GIRK2 constructs The Journal of physiology High 19470775
1997 GIRK2 knockout mice develop spontaneous seizures and are more susceptible to pharmacologically induced seizures (GABA antagonist), demonstrating that GIRK2 is required for normal neuronal excitability. GIRK2-null mice have normal cerebellar morphology but dramatically reduced GIRK1 expression in brain, unlike weaver mice. Weaver heterozygotes show milder cerebellar abnormalities than homozygotes, establishing a dosage-dependent gain-of-function mechanism for the weaver mutation. Gene knockout (homologous recombination), behavioral seizure testing, pharmacological seizure induction, immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 9023358
2002 GIRK2 knockout mice showed largely eliminated clonidine antinociception and significantly reduced morphine antinociception, establishing that postsynaptic GIRK2-mediated signaling is the primary effector for α2-adrenergic receptor analgesia and a major contributor to opioid analgesia. GIRK2 deletion eliminated sex differences in pain threshold, with greater impact in male mice. GIRK2 knockout mice; spinal reflex nociceptive testing (tail-flick); intrathecal drug administration Proceedings of the National Academy of Sciences of the United States of America High 12496346
2002 GIRK2 knockout reduces or eliminates antinociceptive effects of ethanol, oxotremorine, nicotine, baclofen, clonidine, and cannabinoid agonist WIN 55,212 (but not ketamine), establishing that opioid, α-adrenergic, muscarinic cholinergic, GABAB, and cannabinoid receptors are coupled to postsynaptic GIRK2 channels in vivo. GIRK2 also mediates the opioid-dependent component of stress-induced analgesia. GIRK2 knockout mice; hot plate analgesia test; stress-induced analgesia paradigm Proceedings of the National Academy of Sciences of the United States of America High 12493843
2002 In locus coeruleus neurons, acute opioid-induced hyperpolarization is mediated primarily by G-protein-gated K+ channels containing Kir3.2 (GIRK2) and Kir3.3 subunits. [Met5]enkephalin-induced hyperpolarization was reduced by 40% in Kir3.2 KO neurons and by 80% in Kir3.2/Kir3.3 double KO neurons, with residual current nearly eliminated by K+ channel blockers Ba2+/Cs2+. This established that the cAMP-dependent cation conductance does not contribute significantly to acute opioid inhibition of LC neurons. Brain slice electrophysiology from Kir3.2 KO, Kir3.3 KO, and Kir3.2/3.3 double KO mice The Journal of neuroscience High 12040038
2004 Spinal GIRK channels composed primarily of GIRK1/GIRK2 complexes modulate thermal nociception and mediate a significant component of intrathecal high-dose morphine analgesia. GIRK1 or GIRK2 knockout each reduces expression of the other subunit in spinal cord, confirming physical interaction between subunits. The GIRK channel blocker tertiapin reproduced the knockout phenotype in wild-type mice. GIRK1 and GIRK2 knockout mice; tail-flick thermal nociception test; intrathecal drug delivery; Western blot; tertiapin pharmacology The Journal of neuroscience High 15028774
2006 In hippocampal pyramidal cells, Kir3.2-containing channels are enriched around glutamatergic synapses on dendritic spines and co-cluster with GABAB1 receptors at these sites, while on dendritic shafts Kir3.2 and GABAB1 are largely segregated. This compartment-dependent colocalization suggests that spine Kir3.2 channels preferentially mediate GABA effects while shaft channels are activated by other neurotransmitters. High-resolution immunocytochemistry; quantitative immunogold analysis; SDS-digested freeze-fracture replica immunolabeling (SDS-FRL) The Journal of neuroscience High 16624949
1999 GIRK2 splice variant Kir3.2c binds the PDZ domain-containing scaffolding protein PSD-95 (demonstrated by co-immunoprecipitation), while Kir3.2a does not, providing a mechanism for selective postsynaptic localization of Kir3.2c-containing channels to dendritic membranes. Kir3.2c is specifically localized to acrosomal vesicles in testicular spermatids. Co-immunoprecipitation; immunohistochemistry; heterologous expression in Xenopus oocytes and HEK293T cells The Journal of neuroscience Medium 9920664
2012 Conformational rearrangements at the Gβγ-Kir3.1 (GIRK1) subunit interface upon δ-opioid receptor activation were detected by BRET, with DORs, Gβγ, and Kir3 subunits forming a constitutive complex. Conformational changes at the Gβγ/Kir3 interface were predictive of ligand ability to evoke channel currents, and were lost when Kir3.1 was replaced by a mutant lacking Gβγ-activation sites. GαoA did not directly associate with the channel despite being part of the complex. Bioluminescence resonance energy transfer (BRET) in HEK293 cells; co-immunoprecipitation; pertussis toxin treatment; mutagenesis Molecular pharmacology Medium 23175530
2000 RGS4 (a GTPase-activating protein) reduces basal GIRK1/GIRK2 current, accelerates channel deactivation kinetics, and abolishes the post-agonist reduction of basal conductance seen without RGS4 when co-expressed with kappa-opioid receptor in Xenopus oocytes. This establishes that RGS4 gates the duration and extent of GIRK1/GIRK2 channel activation by controlling G-protein GTPase activity. Co-expression in Xenopus oocytes; two-electrode voltage-clamp electrophysiology Life sciences Medium 11065178
1999 Kappa-opioid receptor couples to GIRK1/GIRK2 heteromeric channels. At nanomolar concentrations, U50488H activates GIRK1/GIRK2 via receptor-mediated pathway; at micromolar concentrations, U50488H, propoxyphene, methadone, and naloxone block GIRK1/GIRK2 by direct voltage-independent channel block (IC50 70 µM for U50488H). Morphine did not block at concentrations up to 1 mM. The related IRK1 channel was not affected. Xenopus oocyte expression; two-electrode voltage-clamp electrophysiology; ion substitution European journal of pharmacology Medium 10607882
1999 GIRK1 rescues the weaver GIRK2 (G156S) phenotype by restoring K+ selectivity and G-protein dependence in a subunit-position-dependent manner. When two GIRK2wv subunits are arranged adjacently in a tetramer, currents remain weaver-like; alternating GIRK1-GIRK2wv tetramers restore wild-type K+-selective currents. This provides a structural basis for selective neuronal vulnerability in weaver mice. Xenopus oocyte expression of tandem dimers and linked tetramers; two-electrode voltage-clamp electrophysiology The Journal of neuroscience Medium 10493734
2015 De novo heterozygous mutations in KCNJ6 (GIRK2) cause Keppen-Lubinsky syndrome. An in-frame deletion (p.Thr152del) and a missense mutation (p.Gly154Ser) in the pore region were identified in three unrelated affected individuals, establishing this condition as a channelopathy caused by severely impaired KCNJ6 channel function. Whole-exome sequencing of three unrelated KPLBS patients; genotype-phenotype correlation with animal model data American journal of human genetics Medium 25620207
2018 A de novo heterozygous KCNJ6 mutation p.Leu171Arg causes a gain-of-function: heterologous expression of mutant GIRK2 produces an aberrant basal inward current that is G-protein-independent, loses K+ selectivity, gains Ca2+ permeability, and is inhibited by the Na+ channel blocker QX-314 (similar to weaver). Expression of GIRK1-GIRK2(L171R) tandem dimer produces no current, suggesting non-functional heterotetramers. Whole-exome sequencing; heterologous expression in Xenopus oocytes or HEK cells; patch-clamp electrophysiology; pharmacological characterization Neuroscience High 29852244
2013 GIRK2 channels are necessary and sufficient for peripheral opioid analgesia. GIRK channels are absent from mouse peripheral sensory neurons but present in human and rat. Transgenic expression of GIRK channels in mouse nociceptors established peripheral opioid signaling and local analgesia. A regulatory element in the rat GIRK2 gene accounts for differential expression in rodent sensory neurons. Transgenic mouse expression of GIRK in nociceptors; in vivo pain behavioral assays; immunohistochemistry in human/rat/mouse sensory neurons; regulatory element analysis EMBO molecular medicine High 23818182
2019 Molecular dynamics simulations using the GIRK2 crystal structure revealed that Na+ ions control the cytosolic (G-loop) gate through an anti-clockwise rotation of the cytoplasmic domain, while Gβγ stabilizes the transmembrane inner helix gate in the open state through a rocking movement of the cytoplasmic domain. Both effects alter channel interaction with PIP2 to stabilize respective open states. All-atom microsecond-scale molecular dynamics simulations based on GIRK2 crystal structures The Journal of biological chemistry Medium 31659119
2020 Native mass spectrometry and fluorescent lipid binding assays showed PIP2 (PIP(4,5)P2) cooperatively binds GIRK2 with Hill coefficient of 2.7. Single mutations at specific Kir3.2 residues distinctly alter PIP isoform selectivity: K64Q alters binding profiles favoring specific PIP(4,5)P2 acyl chains, R92P (equivalent to Kir6.2 residue) causes promiscuous binding, and K194A creates preference for PIP(3,4,5)P3. Native mass spectrometry; fluorescent lipid binding assays; site-directed mutagenesis Biochemistry Medium 32372643
1996 A novel GIRK2 splice variant (GIRK2B) has a shorter C-terminus differing in only the last 8 amino acids from GIRK2A. When co-injected with GIRK1 and m2-receptor in Xenopus oocytes, GIRK2B dramatically enhances acetylcholine-induced inwardly rectifying K+ current, demonstrating it forms functional heteromultimeric G-protein-gated K+ channels with GIRK1. cDNA library cloning; RT-PCR tissue distribution; Xenopus oocyte co-expression electrophysiology Biochemical and biophysical research communications Medium 8573147
2017 GIRK2 isoforms GIRK2a and GIRK2c support comparable somato-dendritic GIRK currents in hippocampal pyramidal neurons, but GIRK2c achieves more uniform subcellular distribution and better supports inhibitory postsynaptic currents in distal dendrites. GIRK2a over-expression additionally enhanced cue fear learning, while both isoforms restored contextual fear learning in Girk2-null pyramidal neurons. Viral-mediated expression of individual GIRK2 isoforms in Girk2-/- hippocampal neurons; patch-clamp electrophysiology; immunofluorescence; fear conditioning behavioral assays Scientific reports Medium 28487514
2008 Transgenic mice overexpressing human KCNJ6 (Kir3.2/GIRK2) show increased Kir3.2 protein in atria (2.5-fold) and enhanced chronotropic responses to muscarinic (carbachol, methoxamine) and adenosinergic (CCPA) stimulation, demonstrating that KCNJ6 overexpression alters cardiac rate control specifically at sino-atrial node and atria. Transgenic mouse model with human KCNJ6; ECG recording under urethane anesthesia; pharmacological challenge Physiological genomics Medium 18303085
2017 Increased Kcnj6 gene dose is necessary for synaptic and cognitive dysfunction in the Ts65Dn mouse model of Down syndrome. Reduction of Kcnj6 from 3 to 2 copies in Ts65Dn mice restored hippocampal Kir3.2 protein to normal levels, improved long-term memory, and rescued short-term and long-term potentiation in the dentate gyrus. Fluoxetine, which suppresses Kir3.2 channels, also rescued synaptic plasticity. Genetic reduction of Kcnj6 copy number in Ts65Dn mice; novel object recognition test; hippocampal slice electrophysiology (STP, LTP); fluoxetine pharmacology Neurobiology of disease High 28342823
2016 Deletion of GIRK2 subunit increases basal firing rate of dorsal raphe neurons and causes desensitization of 5-HT1A receptors, demonstrated by lower sensitivity of dorsal raphe neurons to inhibitory effects of 5-HT1A agonist 8-OH-DPAT and citalopram. GIRK2 knockout mice show a depression-resistant behavioral phenotype. In vivo extracellular recordings from dorsal raphe neurons in GIRK2 KO mice; GIRK channel blocker tertiapin-Q; behavioral depression tests The international journal of neuropsychopharmacology Medium 25956878
2023 GIRK2 expressed in NPY/AgRP neurons stabilizes their excitability; conditional deletion of GIRK2 from AgRP neurons increases their persistent excitability, leading to decreased sympathetic activity and energy expenditure (not food intake), resulting in increased body weight and adiposity. Compromised cold adaptation was also observed. AgRP neuron-selective GIRK2 conditional knockout mice; electrophysiology; metabolic phenotyping; sympathetic activity measurement PLoS biology High 37594983
2014 A novel GIRK2 activator (N5) identified from tethered protein scaffold library selection increases Kir3.2 basal activity by inhibiting clearance of the channel from the cell surface (reducing internalization), rather than affecting core biophysical channel properties. Tethered protein display selection in yeast; functional assay; cell surface expression quantification ACS chemical neuroscience Medium 25028803
2022 KCNJ6 noncoding variants in AUD subjects reduce GIRK2 expression in iPSC-derived glutamatergic neurons, causing increased neurite area and elevated neuronal excitability. Ethanol at intoxicating concentrations induces GIRK2 expression and reverses these functional effects. Ectopic overexpression of GIRK2 alone mimics the ethanol effect to normalize excitability, establishing GIRK2 as the molecular effector linking KCNJ6 variants to altered neuronal excitability and ethanol response. iPSC-derived neurons from AUD patients; single-cell RNA sequencing; patch-clamp electrophysiology; morphological analysis; GIRK2 overexpression Molecular psychiatry Medium 36207584

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium. Cell 368 21962516
1997 Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2. Proceedings of the National Academy of Sciences of the United States of America 291 9023358
2013 X-ray structure of the mammalian GIRK2-βγ G-protein complex. Nature 258 23739333
2007 XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 dimerization. Molecular cell 233 17560374
2000 The survivin-like C. elegans BIR-1 protein acts with the Aurora-like kinase AIR-2 to affect chromosomes and the spindle midzone. Molecular cell 218 10983970
1996 Heteromultimerization of G-protein-gated inwardly rectifying K+ channel proteins GIRK1 and GIRK2 and their altered expression in weaver brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 214 8929423
1999 Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR-1 plays a conserved role in cytokinesis. Current biology : CB 205 10209096
1996 Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells. Neuron 171 8630252
1999 Characterization of G-protein-gated K+ channels composed of Kir3.2 subunits in dopaminergic neurons of the substantia nigra. The Journal of neuroscience : the official journal of the Society for Neuroscience 170 9920664
2002 Contribution of GIRK2-mediated postsynaptic signaling to opiate and alpha 2-adrenergic analgesia and analgesic sex differences. Proceedings of the National Academy of Sciences of the United States of America 169 12496346
2002 G-protein-gated potassium channels containing Kir3.2 and Kir3.3 subunits mediate the acute inhibitory effects of opioids on locus ceruleus neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 163 12040038
2002 A pervasive mechanism for analgesia: activation of GIRK2 channels. Proceedings of the National Academy of Sciences of the United States of America 125 12493843
2006 Compartment-dependent colocalization of Kir3.2-containing K+ channels and GABAB receptors in hippocampal pyramidal cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 120 16624949
2004 Spinal G-protein-gated K+ channels formed by GIRK1 and GIRK2 subunits modulate thermal nociception and contribute to morphine analgesia. The Journal of neuroscience : the official journal of the Society for Neuroscience 116 15028774
2014 Quantitative analysis of mammalian GIRK2 channel regulation by G proteins, the signaling lipid PIP2 and Na+ in a reconstituted system. eLife 109 25049222
2006 A Bir1-Sli15 complex connects centromeres to microtubules and is required to sense kinetochore tension. Cell 103 17174893
2001 Potassium channels as targets for ethanol: studies of G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) null mutant mice. The Journal of pharmacology and experimental therapeutics 98 11454913
1997 Defective gamma-aminobutyric acid type B receptor-activated inwardly rectifying K+ currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice. Proceedings of the National Academy of Sciences of the United States of America 96 9342388
1996 The weaver mutation of GIRK2 results in a loss of inwardly rectifying K+ current in cerebellar granule cells. Proceedings of the National Academy of Sciences of the United States of America 96 8855331
2015 Keppen-Lubinsky syndrome is caused by mutations in the inwardly rectifying K+ channel encoded by KCNJ6. American journal of human genetics 92 25620207
2000 Functional and biochemical evidence for G-protein-gated inwardly rectifying K+ (GIRK) channels composed of GIRK2 and GIRK3. The Journal of biological chemistry 88 10956667
2001 Bir1/Cut17 moving from chromosome to spindle upon the loss of cohesion is required for condensation, spindle elongation and repair. Genes to cells : devoted to molecular & cellular mechanisms 85 11554922
2003 CSC-1: a subunit of the Aurora B kinase complex that binds to the survivin-like protein BIR-1 and the incenp-like protein ICP-1. The Journal of cell biology 83 12707312
2012 GIRK2 expression in dopamine neurons of the substantia nigra and ventral tegmental area. The Journal of comparative neurology 82 22252428
1997 An immunocytochemical study on the distribution of two G-protein-gated inward rectifier potassium channels (GIRK2 and GIRK4) in the adult rat brain. Neuroscience 76 9284339
2013 The K(+) channel GIRK2 is both necessary and sufficient for peripheral opioid-mediated analgesia. EMBO molecular medicine 74 23818182
1998 Girk2 expression in the ventral midbrain, cerebellum, and olfactory bulb and its relationship to the murine mutation weaver. Developmental biology 74 9882481
2006 Abnormal expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in hippocampus, frontal cortex, and substantia nigra of Ts65Dn mouse: a model of Down syndrome. The Journal of comparative neurology 71 16374808
2000 Cell division regulation by BIR1, a member of the inhibitor of apoptosis family in yeast. The Journal of biological chemistry 67 10702224
2012 Trisomy of the G protein-coupled K+ channel gene, Kcnj6, affects reward mechanisms, cognitive functions, and synaptic plasticity in mice. Proceedings of the National Academy of Sciences of the United States of America 64 22308328
2003 Mapping the Gbetagamma-binding sites in GIRK1 and GIRK2 subunits of the G protein-activated K+ channel. The Journal of biological chemistry 63 12743112
2009 Association between KCNJ6 (GIRK2) gene polymorphisms and postoperative analgesic requirements after major abdominal surgery. PloS one 58 19756153
2001 GIRK2 deficient mice. Evidence for hyperactivity and reduced anxiety. Physiology & behavior 58 11564458
2016 Cooperative regulation by G proteins and Na(+) of neuronal GIRK2 K(+) channels. eLife 52 27074662
1996 A novel ubiquitously distributed isoform of GIRK2 (GIRK2B) enhances GIRK1 expression of the G-protein-gated K+ current in Xenopus oocytes. Biochemical and biophysical research communications 51 8573147
2010 Clinical manifestations of the deletion of Down syndrome critical region including DYRK1A and KCNJ6. American journal of medical genetics. Part A 49 21204217
1996 The weaver mutation changes the ion selectivity of the affected inwardly rectifying potassium channel GIRK2. FEBS letters 49 8706831
2009 Divergent regulation of GIRK1 and GIRK2 subunits of the neuronal G protein gated K+ channel by GalphaiGDP and Gbetagamma. The Journal of physiology 46 19470775
1999 Molecular cloning and characterization of a novel splicing variant of the Kir3.2 subunit predominantly expressed in mouse testis. The Journal of physiology 46 10562331
1998 Characterization of murine Girk2 transcript isoforms: structure and differential expression. Genomics 45 9721208
2012 Conformational dynamics of Kir3.1/Kir3.2 channel activation via δ-opioid receptors. Molecular pharmacology 44 23175530
1995 Characterization and variation of a human inwardly-rectifying-K-channel gene (KCNJ6): a putative ATP-sensitive K-channel subunit. FEBS letters 44 7796919
2010 A KCNJ6 (Kir3.2, GIRK2) gene polymorphism modulates opioid effects on analgesia and addiction but not on pupil size. Pharmacogenetics and genomics 43 20220551
2010 GABAB-GIRK2-mediated signaling in Down syndrome. Advances in pharmacology (San Diego, Calif.) 43 20655490
2013 Associations between KCNJ6 (GIRK2) gene polymorphisms and pain-related phenotypes. Pain 40 23994450
2014 Association between KCNJ6 (GIRK2) gene polymorphism rs2835859 and post-operative analgesia, pain sensitivity, and nicotine dependence. Journal of pharmacological sciences 39 25346042
2019 On the mechanism of GIRK2 channel gating by phosphatidylinositol bisphosphate, sodium, and the Gβγ dimer. The Journal of biological chemistry 37 31659119
2005 Phosphorylation of the chromosomal passenger protein Bir1 is required for localization of Ndc10 to the spindle during anaphase and full spindle elongation. Molecular biology of the cell 37 16381814
2021 Structural insights into GIRK2 channel modulation by cholesterol and PIP2. Cell reports 36 34433062
2017 Evidence that increased Kcnj6 gene dose is necessary for deficits in behavior and dentate gyrus synaptic plasticity in the Ts65Dn mouse model of Down syndrome. Neurobiology of disease 36 28342823
2011 KCNJ6 is associated with adult alcohol dependence and involved in gene × early life stress interactions in adolescent alcohol drinking. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 36 21307845
1995 Assessment of a mutation in the H5 domain of Girk2 as a candidate for the weaver mutation. Genome research 35 8808466
2006 Elevated expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in cerebellar unipolar brush cells of a Down syndrome mouse model. Cellular and molecular neurobiology 34 16783527
2005 G-protein-gated potassium (GIRK) channels containing the GIRK2 subunit are control hubs for pharmacologically induced hypothermic responses. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 16120781
1997 Comparative expression of the inward rectifier K+ channel GIRK2 in the cerebellum of normal and weaver mutant mice. Brain research 31 9125426
2003 Mutation of KCNK5 or Kir3.2 potassium channels in mice does not change minimum alveolar anesthetic concentration. Anesthesia and analgesia 30 12707131
2001 Hyperactivity and dopamine D1 receptor activation in mice lacking girk2 channels. Psychopharmacology 30 11823889
2015 Deletion of GIRK2 Subunit of GIRK Channels Alters the 5-HT1A Receptor-Mediated Signaling and Results in a Depression-Resistant Behavior. The international journal of neuropsychopharmacology 28 25956878
1999 The dual modulation of GIRK1/GIRK2 channels by opioid receptor ligands. European journal of pharmacology 27 10607882
2009 TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-kappaB. Oncogene 26 19234489
2007 Crystal structure of the BIR1 domain of XIAP in two crystal forms. Journal of molecular biology 25 17698078
2014 Regulation of SOBIR1 accumulation and activation of defense responses in bir1-1 by specific components of ER quality control. The Plant journal : for cell and molecular biology 24 24498907
1997 In situ hybridization analysis of Girk2 expression in the developing central nervous system in normal and weaver mice. Journal of neuropathology and experimental neurology 23 9210872
2019 The immune repressor BIR1 contributes to antiviral defense and undergoes transcriptional and post-transcriptional regulation during viral infections. The New phytologist 22 31111491
2010 Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 22 20943350
2024 Calbindin and Girk2/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate Parkinson's disease model. NPJ Parkinson's disease 21 39223183
2018 Gain-of-function KCNJ6 Mutation in a Severe Hyperkinetic Movement Disorder Phenotype. Neuroscience 21 29852244
2016 Infantile spasms in down syndrome: Rescue by knockdown of the GIRK2 channel. Annals of neurology 21 27462820
2017 GIRK2 splice variants and neuronal G protein-gated K+ channels: implications for channel function and behavior. Scientific reports 20 28487514
2015 The GIRK2 subunit is involved in IS-like seizures induced by GABA(B) receptor agonists. Epilepsia 20 26032891
1995 Cloning of rat KATP-2 channel and decreased expression in pancreatic islets of male Zucker diabetic fatty rats. Biochemical and biophysical research communications 20 7626127
2020 Insight into the Selectivity of Kir3.2 toward Phosphatidylinositides. Biochemistry 19 32372643
2000 Changes in GIRK1/GIRK2 deactivation kinetics and basal activity in the presence and absence of RGS4. Life sciences 19 11065178
1995 Distribution of mRNA encoding the inwardly rectifying K+ channel, BIR1 in rat tissues. FEBS letters 19 7589501
2022 Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons. Molecular psychiatry 17 36207584
2009 Efficient chromosome biorientation and the tension checkpoint in Saccharomyces cerevisiae both require Bir1. Molecular and cellular biology 17 19528231
2016 A KCNJ6 gene polymorphism modulates theta oscillations during reward processing. International journal of psychophysiology : official journal of the International Organization of Psychophysiology 16 27993610
1999 Alteration in expression of G-protein-activated inward rectifier K+-channel subunits GIRK1 and GIRK2 in the rat brain following electroconvulsive shock. Neuroscience 16 10215164
2018 Kcnj6(GIRK2) trisomy is not sufficient for conferring the susceptibility to infantile spasms seen in the Ts65Dn mouse model of down syndrome. Epilepsy research 15 29929098
2012 Role of GIRK channels on the noradrenergic transmission in vivo: an electrophysiological and neurochemical study on GIRK2 mutant mice. The international journal of neuropsychopharmacology 15 23040084
1997 An immunocytochemical study of a G-protein-gated inward rectifier K+ channel (GIRK2) in the weaver mouse mesencephalon. Neuroreport 15 9141074
2015 ER quality control components UGGT and STT3a are required for activation of defense responses in bir1-1. PloS one 14 25775181
2012 Bir1 deletion causes malfunction of the spindle assembly checkpoint and apoptosis in yeast. Frontiers in oncology 14 22908045
2000 Mutation analysis of the inwardly rectifying K(+) channels KCNJ6 (GIRK2) and KCNJ3 (GIRK1) in juvenile myoclonic epilepsy. American journal of medical genetics 14 10686544
2019 KCNJ6 variants modulate reward-related brain processes and impact executive functions in attention-deficit/hyperactivity disorder. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 13 31099984
2008 Altered heart rate control in transgenic mice carrying the KCNJ6 gene of the human chromosome 21. Physiological genomics 12 18303085
1999 The weaver GIRK2 mutation leads to decreased levels of serum thyroid hormone: characterization of the effect on midbrain dopaminergic neuron survival. Experimental neurology 12 10619558
2016 Molecular dynamics of the honey bee toxin tertiapin binding to Kir3.2. Biophysical chemistry 11 27716538
2012 Conductance properties of the inwardly rectifying channel, Kir3.2: molecular and Brownian dynamics study. Biochimica et biophysica acta 11 23022491
2003 BIR-1, a Caenorhabditis elegans homologue of Survivin, regulates transcription and development. Proceedings of the National Academy of Sciences of the United States of America 10 12682297
2012 Differential maturation of GIRK2-expressing neurons in the mouse cerebellum. Journal of chemical neuroanatomy 9 23261870
1999 The inwardly rectifying K(+) channel subunit GIRK1 rescues the GIRK2 weaver phenotype. The Journal of neuroscience : the official journal of the Society for Neuroscience 9 10493734
2022 GIRK2 Channels in Down Syndrome and Alzheimer's Disease. Current Alzheimer research 8 36567290
2021 Structural Characterization of the Highly Restricted Down Syndrome Critical Region on 21q22.13: New KCNJ6 and DSCR4 Transcript Isoforms. Frontiers in genetics 8 34956324
2020 Permeation mechanisms through the selectivity filter and the open helix bundle crossing gate of GIRK2. Computational and structural biotechnology journal 8 33335691
2015 NF023 binding to XIAP-BIR1: searching drugs for regulation of the NF-κB pathway. Proteins 8 25619915
2001 The expression of G-protein-gated inwardly rectifying K+ channels GIRK1 and GIRK2 mRNAs in the supraoptic nucleus of the rat and possible role involved. Neuroreport 8 11303735
2000 Involvement of GIRK2 in postnatal development of the weaver cerebellum. Journal of neuroscience research 8 10740221
2023 GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice. PLoS biology 7 37594983
2014 Tethered protein display identifies a novel Kir3.2 (GIRK2) regulator from protein scaffold libraries. ACS chemical neuroscience 7 25028803

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