Affinage

KCNJ3

G protein-activated inward rectifier potassium channel 1 · UniProt P48549

Length
501 aa
Mass
56.6 kDa
Annotated
2026-04-28
100 papers in source corpus 48 papers cited in narrative 48 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNJ3 (Kir3.1/GIRK1) encodes an obligate heteromeric subunit of G protein-gated inwardly rectifying potassium (GIRK) channels that mediates inhibitory signaling downstream of Gi/o-coupled receptors in heart and brain. GIRK1 assembles with GIRK2 or GIRK4 to form functional heterotetramers; GIRK1 alone cannot reach the plasma membrane or form efficient homomeric channels, but its unique pore-loop residues and distal C-terminus confer high basal activity, enhanced Gβγ responsiveness, and a Gβγ-anchoring function distinct from the activation site (PMID:8789957, PMID:25384780, PMID:27074664). Gβγ binds directly to both N- and C-terminal cytoplasmic domains of GIRK1 at inter-subunit interfaces with a stoichiometry of four Gβγ per tetramer, inducing conformational changes that open a cytoplasmic G-loop gate and a selectivity-filter gate, while PIP2 is absolutely required for channel activity and PKA phosphorylation enhances open probability (PMID:7576656, PMID:21075842, PMID:15723059, PMID:20937804, PMID:12547819). Knockout of GIRK1 abolishes atrial IKACh currents causing mild resting tachycardia, produces thermal hyperalgesia and reduced opioid analgesia in the spinal cord, and a gain-of-function KCNJ3 mutation (p.N83H) causes constitutive IKACh activation leading to bradyarrhythmia (PMID:12374786, PMID:15028774, PMID:30764634).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 High

    Establishing that Gβγ directly binds GIRK1 cytoplasmic domains resolved the longstanding question of how G protein-coupled receptors gate inward rectifier K+ channels — the mechanism is direct protein-protein interaction rather than a diffusible second messenger.

    Evidence Pulldown binding assays, peptide competition, and electrophysiology in Xenopus oocytes; confirmed by GST-fusion binding with purified Gβγ and GDP-Gα competition

    PMID:7576656 PMID:7626088

    Open questions at the time
    • Atomic structure of the Gβγ–GIRK1 complex not yet determined
    • Stoichiometry of Gβγ binding per channel unknown at this stage
  2. 1995 High

    Chimera analysis localized Gβγ sensitivity to the cytoplasmic N- and C-terminal domains of GIRK1, separating the G protein-coupling mechanism from the pore-forming transmembrane core that determines conductance properties.

    Evidence GIRK1/IRK1 chimeras expressed in Xenopus oocytes with electrophysiology

    PMID:7576657

    Open questions at the time
    • Specific residues mediating Gβγ activation not yet identified
    • Whether N- and C-terminal sites function independently or cooperatively unclear
  3. 1996 High

    Demonstration that GIRK1 requires a partner subunit (GIRK2 or GIRK4/CIR) for both surface trafficking and functional channel formation established the obligate heteromeric nature of GIRK1-containing channels.

    Evidence Co-IP from native brain tissue showing GIRK1-GIRK2 association; antisense knockdown of endogenous XIR reducing GIRK1 currents by 80%; immunofluorescence showing GIRK1 retention at intracellular sites without CIR

    PMID:8789957 PMID:8929423 PMID:8938714

    Open questions at the time
    • Molecular determinants of heteromeric assembly not mapped
    • Whether GIRK1 can form any functional homomeric channels under physiological conditions
  4. 1997 Medium

    Identification of the GIRK1 distal C-terminus as an intrinsic gating element and of RGS4 as a temporal regulator of GIRK deactivation defined both channel-intrinsic and extrinsic mechanisms controlling GIRK gating kinetics.

    Evidence C-terminal peptide DS6 blocks GIRK in inside-out patches; RGS4 co-expression accelerates deactivation in oocytes; F137S mutation enables functional homomers revealing conserved G protein coupling sites

    PMID:11065178 PMID:9395492 PMID:9409468

    Open questions at the time
    • DS6 peptide blocking mechanism not validated in native channels
    • RGS4 interaction site on the signaling complex not mapped
  5. 2000 High

    Discovery that polyamine unbinding from pore-lining charged residues accounts for slow activation kinetics, and that PKC/Gq-coupled receptor signaling suppresses GIRK1/4 currents, revealed that inward rectification and cross-talk between Gi and Gq pathways converge on channel gating.

    Evidence Mutagenesis of H5/M2/C-terminal charged residues with polyamine reconstitution in excised patches; Gq-mediated suppression via PKC dissected pharmacologically in oocytes

    PMID:10956662 PMID:11060307

    Open questions at the time
    • Exact PKC phosphorylation sites on the channel unknown
    • Molecular mechanism of Gq-PKC inhibition not resolved
  6. 2002 High

    The crystal structure of the GIRK1 cytoplasmic pore provided the first atomic view of the inward-rectifier ion permeation pathway, revealing how polyamines and acidic residues create inward rectification, while GIRK1 knockout mice proved the subunit is essential for cardiac IKACh.

    Evidence 1.8 Å X-ray structure of cytoplasmic domains; GIRK1-knockout mice with loss of atrial IKACh and mild tachycardia

    PMID:12374786 PMID:12507423

    Open questions at the time
    • Full-length channel structure not yet available
    • Contribution of GIRK1 versus GIRK4 to native cardiac IKACh stoichiometry not fully resolved
  7. 2003 High

    Mapping of Gβγ-binding segments and identification of critical leucine residues distinguished binding from gating transduction, while PKA phosphorylation was shown to enhance GIRK1/4 open probability by releasing channels from long-closed states, defining a phosphorylation-dependent regulatory layer.

    Evidence GST pulldown binding with mutagenesis identifying L262/L333 for gating; single-channel electrophysiology with PKA/PP2A application to excised patches; selectivity filter mutagenesis correlating K+ selectivity with agonist gating

    PMID:12547819 PMID:12743112 PMID:14504281 PMID:14525972

    Open questions at the time
    • Whether PKA and Gβγ act synergistically at the structural level unknown
    • Selectivity filter gating model lacks direct structural evidence
  8. 2004 High

    Discovery that GIRK1/GIRK2 heteromers mediate spinal thermal nociception and opioid analgesia, and that IKACh channels exist in a multi-protein signaling complex with kinases and phosphatases, broadened the physiological role of GIRK1 beyond the heart.

    Evidence GIRK1 and GIRK2 knockout mice with hyperalgesia and reduced morphine analgesia; co-IP from atrial tissue identifying PKA, PP1, PP2A, RACK1, GRK in complex with GIRK1/4

    PMID:15028774 PMID:15037627

    Open questions at the time
    • Identity of the kinase/phosphatase targets on the channel within the native complex
    • Whether GIRK1/2 and GIRK1/4 complexes have different macromolecular compositions
  9. 2005 High

    Identification of the G-loop as a cytoplasmic gate and PKC-δ as the specific isoform mediating Gq-dependent GIRK inhibition resolved the structural and enzymatic basis of two key regulatory mechanisms.

    Evidence Crystal structure of cytoplasmic domain identifying G-loop occlusion with mutagenesis validation; inside-out patch application of active PKC-δ, dominant-negative PKC-δ, and phosphatase reversal

    PMID:15723059 PMID:15857907

    Open questions at the time
    • How Gβγ binding opens the G-loop gate structurally
    • PKC-δ phosphorylation site(s) on GIRK subunits not identified
  10. 2006 High

    Demonstration that GIRK1 exists in pre-assembled complexes with heterotrimeric G proteins and GPCRs that form before reaching the plasma membrane replaced the collision-coupling model with a conformational signaling model for GIRK activation.

    Evidence BRET, co-IP, and BiFC showing stable GIRK1–Gαβγ complexes; BRET increase upon agonist stimulation without complex dissociation

    PMID:16787947

    Open questions at the time
    • Structural basis of conformational change within the pre-assembled complex unknown
    • Stoichiometry of G protein subunits per pre-assembled complex not resolved
  11. 2007 High

    Crystal structures of a GIRK1 chimera in open-like and closed conformations revealed PIP2-interacting residues and showed that gating involves rigid-body subunit rotations at both the inner helix bundle and cytoplasmic apex.

    Evidence 2.2 Å X-ray structures of Kir3.1-KirBac1.3 chimera in two conformations

    PMID:17703190

    Open questions at the time
    • Chimera may not recapitulate all gating properties of native heterotetramers
    • PIP2-bound structure not captured
  12. 2010 High

    Quantitative biophysical measurements established that four Gβγ bind per GIRK1 tetramer at inter-subunit interfaces and that PIP2 is absolutely required for reconstituted channel activity, providing the stoichiometric and lipid framework for activation.

    Evidence ITC and NMR of GIRK1 cytoplasmic domain with Gβγ; planar lipid bilayer reconstitution of chimeric channels requiring PIP2

    PMID:20937804 PMID:21075842

    Open questions at the time
    • Kd of ~250 μM measured with isolated cytoplasmic domains may differ in full-length channel
    • Cooperativity of Gβγ binding across four sites not fully characterized
  13. 2012 High

    BRET studies tracking conformational changes from receptor through Gβγ to GIRK1 demonstrated that agonist efficacy is transmitted as conformational information along pre-assembled signaling complexes, while systematic mutagenesis of GIRK1 pore residues identified determinants of the subunit's unique potentiating effect on channel activity.

    Evidence Multi-pair BRET with DOR/Gβγ/Kir3 subunits; systematic mutagenesis of P-loop (F137, A142, Y150) and distal C-terminus (Q404) with single-channel analysis

    PMID:23175530 PMID:23236146

    Open questions at the time
    • Whether the conformational relay operates identically for different receptor types
    • Structural basis for P-loop residue potentiation not resolved
  14. 2013 High

    Computational docking validated by disulfide cross-linking defined the Gβγ binding interface on GIRK1 at the LM/DE loop cleft, while PKA phosphorylation sites were mapped on both GIRK1 and GIRK4 subunits, completing the molecular map of the two major positive regulatory inputs.

    Evidence Protein-protein docking with reciprocal mutagenesis and constitutive-activation by engineered disulfides; PKA site identification by mutagenesis (S385, S401, T407) and in vitro phosphorylation

    PMID:23305758 PMID:23943609

    Open questions at the time
    • No cryo-EM or crystal structure of the full Gβγ–GIRK complex
    • Whether individual PKA sites are phosphorylated sequentially or simultaneously
  15. 2014 High

    Identification of the GIRK1 distal C-terminus as a distinct Gβγ-anchoring domain (separate from the activation site) and quantitative modeling of Gβγ/Gα stoichiometry (4 Gβγ and ≤2 Gαi/o per channel) refined the mechanistic model of how the pre-assembled signaling complex is organized.

    Evidence Truncation mutants with fluorescence and biochemistry showing Gβγ recruitment function; quantitative modeling validated in oocytes, HEK293, and hippocampal neurons

    PMID:25384780 PMID:26544551

    Open questions at the time
    • Whether the anchoring C-terminus contacts Gα in the heterotrimer
    • Structural basis for asymmetric Gα stoichiometry not explained
  16. 2016 High

    Reconstitution of purified GIRK1/4 heterotetramers revealed that GIRK1 functionally mimics a Na+-activated GIRK4 subunit, explaining why incorporation of GIRK1 confers constitutively high Gβγ responsiveness without Na+ sensitivity.

    Evidence Purified protein reconstitution in lipid bilayers with single-channel comparison of homo- and heterotetramers

    PMID:27074664

    Open questions at the time
    • Structural basis for the defective Na+ site in GIRK1 not visualized
    • Whether this mechanism applies equally to GIRK1/2 heterotetramers
  17. 2019 High

    A gain-of-function KCNJ3 mutation (p.N83H) causing constitutive IKACh activation and bradyarrhythmia, rescued by IKACh blocker NIP-151, provided human disease relevance and pharmacological proof of concept for GIRK1 channel targeting.

    Evidence Cellular electrophysiology of N83H mutant, transgenic zebrafish model, pharmacological rescue

    PMID:30764634

    Open questions at the time
    • Whether this mutation is identified in human familial arrhythmia pedigrees
    • Mechanism by which N83H increases basal activity not structurally resolved
  18. 2020 High

    Discovery of GAT1508, a subunit-selective allosteric GIRK1/2 activator acting at a mutagenesis-validated GIRK1 binding site to modulate PIP2 interaction, demonstrated that GIRK1-containing channels are druggable targets for CNS disorders.

    Evidence Chemical screen, mutagenesis validation, brain-slice electrophysiology in basolateral amygdala, fear extinction behavioral assay in rodents

    PMID:31953327

    Open questions at the time
    • Co-crystal or cryo-EM structure of GAT1508 bound to GIRK1/2 not available
    • Long-term safety and selectivity in vivo not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the full-length native GIRK1/2 or GIRK1/4 heterotetramer in complex with Gβγ and PIP2 remains unavailable, leaving the integrative gating mechanism — how Gβγ binding, PIP2 interaction, and phosphorylation collectively open both the G-loop and selectivity filter gates — structurally unresolved.
  • No full-length GIRK1-containing heterotetramer structure with bound Gβγ
  • Allosteric coupling between G-loop gate and selectivity filter gate not mechanistically resolved
  • In vivo phosphorylation dynamics of GIRK1 in cardiac and neuronal contexts poorly characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 4 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-382551 Transport of small molecules 4 R-HSA-112316 Neuronal System 3
Partners
GNAI3GNB1GNG2KCNJ2KCNJ5KCNJ6KCNJ9RGS4
Complex memberships
GIRK1/GIRK2 (Kir3.1/Kir3.2) heterotetramerGIRK1/GIRK3 (Kir3.1/Kir3.3) heterotetramerGIRK1/GIRK4 (Kir3.1/Kir3.4) heterotetramer (IKACh)

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Crystal structure of the cytoplasmic pore of GIRK1 (Kir3.1) at 1.8 Å resolution revealed a cytoplasmic ion pathway ~60 Å long, lined by acidic and hydrophobic residues that create a favorable environment for polyamine block, explaining the structural and chemical basis of inward rectification. X-ray crystallography of cytoplasmic N- and C-terminal domains Cell High 12507423
2007 Crystal structure of a Kir3.1-prokaryotic Kir chimera at 2.2 Å identified two constrictions (inner helix bundle and apex of cytoplasmic pore) as potential gates, and identified PIP2-interacting residues on the cytoplasmic pore that regulate gating; gating of the cytoplasmic apex is mediated by rigid-body subunit movements. X-ray crystallography of Kir3.1-KirBac1.3 chimera expressed in E. coli The EMBO journal High 17703190
2005 Crystal structure of the cytoplasmic domain of Kir3.1 (Kir3.1S) showed that four cytoplasmic loops form a 'G-loop' girdle that occludes the cytoplasmic ion permeation pathway; G-loop mutations disrupted gating, implicating it as a diffusion barrier/gate between the cytoplasmic and transmembrane pores. X-ray crystallography + site-directed mutagenesis of G-loop residues Nature neuroscience High 15723059
1995 Gβγ directly binds to both the N-terminal hydrophilic domain and amino acids 273–462 of the C-terminal domain of GIRK1; synthetic peptides from either domain reduce Gβγ binding and Gβγ-mediated channel activation, establishing direct Gβγ–GIRK1 interaction as the mechanism of channel activation. Direct binding assays (pulldown), peptide competition, electrophysiology in Xenopus oocytes Neuron High 7576656
1995 Gβγ directly binds to the C-terminus of GIRK1; GDP-bound Gα inhibits this binding, while GTPγS-activated Gα does not, consistent with the model that Gβγ released from Gα upon receptor activation gates the channel. GST pulldown of purified Gβγ to GIRK1 C-terminal fusion protein Biochemical and biophysical research communications High 7626088
1995 Chimera analysis of GIRK1 and the G protein-insensitive IRK1 identified that either the N-terminal or part of the C-terminal hydrophilic domain of GIRK1 is sufficient to confer Gβγ sensitivity, and that the hydrophobic core (M1-H5-M2) determines single-channel open times but not Gβγ sensitivity. GIRK1/IRK1 chimeras expressed in Xenopus oocytes, electrophysiology Neuron High 7576657
1996 GIRK1 and GIRK2 co-immunoprecipitate from brain regions where both are expressed, demonstrating they physically interact to form heteromeric channels in vivo; in the weaver mouse, loss of GIRK2 is accompanied by dramatic reduction of GIRK1 expression in overlapping regions, consistent with co-assembly-dependent stability. Co-immunoprecipitation from rat/mouse brain tissue, immunohistochemistry The Journal of neuroscience High 8929423
1996 GIRK1 forms functional heteromeric channels with the endogenous Xenopus oocyte subunit XIR (a CIR homolog); antisense knockdown of XIR reduces GIRK1-dependent currents by 80%, establishing that GIRK1 does not efficiently form functional homomeric channels and requires a partner subunit. Antisense oligonucleotide knockdown of endogenous XIR in Xenopus oocytes + electrophysiology Neuron High 8789957
2002 Kir3.1 (GIRK1) knockout mice show loss of carbachol-induced IKACh current in atrial myocytes and mild resting tachycardia, demonstrating that Kir3.1 is required for functional IKACh channel activity; residual Kir3.4 homomultimer activity is minimal and unstable, confirming Kir3.1's role in enhancing channel activity. Knockout mouse model, patch-clamp electrophysiology of atrial myocytes The Journal of biological chemistry High 12374786
2003 Gβγ-binding sites in GIRK1 were mapped to the N-terminus and two segments of the C-terminus (including a previously unrecognized segment in the first half and a major site between residues ~320–409); C-terminal leucines L262 and L333 are critical for Gβγ-induced gating changes rather than Gβγ binding per se. GST pulldown binding assays, Gαi1 competition assay, mutagenesis + electrophysiology in Xenopus oocytes The Journal of biological chemistry High 12743112
2004 Spinal GIRK channels composed primarily of GIRK1/GIRK2 heteromers modulate thermal nociception; GIRK1 knockout mice exhibit hyperalgesia in the tail-flick test and decreased analgesic response to intrathecal high-dose morphine, and loss of either subunit reduces expression of the other, indicating physical interaction. GIRK1 and GIRK2 knockout mice, tail-flick behavioral test, intrathecal morphine analgesia, protein expression analysis The Journal of neuroscience High 15028774
2010 NMR and ITC analyses showed that four Gβγ molecules bind per GIRK1 cytoplasmic pore tetramer (Kd ~250 μM) and that the Gβγ binding site spans two neighboring subunits, inducing inter-subunit conformational rearrangements consistent with channel gate opening. Isothermal titration calorimetry (ITC) and NMR spectroscopy of GIRK1 cytoplasmic domain The Journal of biological chemistry High 21075842
2016 Using purified proteins in lipid bilayers, GIRK1/4 heterotetramers were found to be unresponsive to Na+ activation (unlike GIRK4 homotetramers), but display constitutively high responsiveness to Gβγ, suggesting that the GIRK1 subunit (with defective Na+ site) mimics a GIRK4 subunit with Na+ permanently bound, thereby potentiating G protein responsiveness. Purified protein reconstitution in lipid bilayers, single-channel electrophysiology eLife High 27074664
2013 Computational docking and reciprocal mutagenesis showed that Gβ interacts with GIRK1 at a cleft between adjacent subunits formed by the LM and DE loops; disulfide cross-linking of cysteine mutants at predicted interface residues yielded constitutively activated channels, confirming the binding mode and activation mechanism. Protein-protein docking, mutagenesis, disulfide cross-linking, electrophysiology in Xenopus oocytes Science signaling High 23943609
2010 Functional reconstitution of the Kir3.1-KirBac1.3 chimera in planar lipid bilayers showed absolute requirement for PIP2 for channel activity, Mg2+-dependent inward rectification, and stimulation by both activated Gα and Gβγ (both required together for full gating), confirming these as direct regulators. Reconstitution in planar lipid bilayers, single-particle electron microscopy The Journal of biological chemistry High 20937804
1997 Functional homomeric GIRK1(F137S) mutant channels confirmed that GIRK1 and GIRK4 subunits interact with G protein subunits through qualitatively similar, homologous regions rather than through their divergent terminal domains; Gβγ plays a crucial but not exclusive activating role for both subunits. Site-directed mutagenesis generating functional homomers, coexpression with G protein subunits and receptors in Xenopus oocytes, electrophysiology The Journal of biological chemistry High 9395492
2009 GDP-bound Gαi3 (inactive form) specifically regulates GIRK1-containing channels by reducing basal activity and enhancing Gβγ-evoked activation through a mechanism requiring the unique distal C-terminus of GIRK1; this regulation was not observed in GIRK2 homotetramers, and purified Gβγ enhanced Gαi3GDP binding to GIRK1 but not GIRK2 cytosolic domains. Electrophysiology in Xenopus oocytes, in vitro protein interaction (pulldown with purified components), chimeric and point-mutant channels The Journal of physiology High 19470775
2014 The distal C-terminus of GIRK1 (G1-dCT) recruits Gβγ to the plasma membrane and is required for high basal channel activity; truncation of G1-dCT reduces GIRK1–Gβγ binding in biochemical assays and abolishes Gβγ recruitment and basal current without impairing Gβγ-evoked activation, identifying G1-dCT as a Gβγ anchoring site functionally distinct from the activation site. Electrophysiology in Xenopus oocytes, fluorescence membrane density assays, biochemical binding assays with truncation mutants The Journal of physiology High 25384780
2004 Atrial GIRK1/GIRK4 (KACh) channels are assembled in a signaling complex with Gβγ, GRK, PKA, PP1, PP2A, RACK1, and actin; PKC activation potently inhibits Gβγ-induced KACh channel activity, demonstrating that this complex serves as a spatial integrator of multiple signaling pathways. Co-immunoprecipitation from atrial tissue, single-channel electrophysiology with kinase/phosphatase application The Journal of biological chemistry High 15037627
2006 BRET and co-immunoprecipitation showed that heterotrimeric G proteins (Gαs, Gαi, Gβ1, Gγ2) and Kir3.1 form stable pre-assembled complexes that persist during signaling; receptor stimulation increases BRET between Gβγ and Kir3.1 without dissociating the complex, indicating conformational rather than dissociation-based activation; complexes form before transport to the plasma membrane. BRET, co-immunoprecipitation, BiFC (split-YFP) in living cells Journal of cell science High 16787947
2012 BRET and co-immunoprecipitation showed that δ-opioid receptors (DORs), Gβγ, and Kir3.1/Kir3.2 subunits constitutively interact; agonist-induced conformational changes at the Gβγ–Kir3.1 interface follow the same kinetics and efficacy order as changes at the receptor–Gβγ and Gα–Gβγ interfaces and are lost when Kir3.1 lacks essential Gβγ activation sites, establishing that conformational information is relayed from receptor to channel via Gβγ repositioning. BRET, co-immunoprecipitation, electrophysiology in HEK293 cells Molecular pharmacology High 23175530
2010 GABAB receptors form stable complexes with GIRK1/GIRK3 heterotetramers, detected by BRET, co-immunoprecipitation, and electron microscopy in both heterologous cells and native cerebellar granule cells; complex formation occurs shortly after biosynthesis, likely in the ER/Golgi. BRET, co-immunoprecipitation, confocal and electron microscopy The European journal of neuroscience High 20846323
2003 Mutation of charged glutamate and arginine residues behind the selectivity filter of Kir3.1/Kir3.4 reduces or abolishes K+ selectivity and eliminates polyamine-induced inward rectification; molecular modeling shows these residues form a salt bridge 'bowstring' that maintains selectivity filter rigidity. Site-directed mutagenesis, electrophysiology, molecular modeling The Journal of biological chemistry High 14504281
2003 Mutations within the selectivity filter of Kir3.1/Kir3.4 that alter K+ selectivity also abolish agonist activation, while non-selectivity-altering mutations do not; this correlation suggests the selectivity filter acts as the agonist-activated gate in this channel. Site-directed mutagenesis of pore residues, electrophysiology The Journal of biological chemistry Medium 14525972
2000 Mutations of negatively charged residues in H5 (near selectivity filter), M2, and proximal C-terminus of Kir3.1/Kir3.4 reduced or abolished slow activation; slow activation was lost upon patch excision and restored by polyamine addition, identifying polyamine unbinding from these residues as the mechanism of slow activation rather than an intrinsic gating process. Site-directed mutagenesis, inside-out and cell-attached patch electrophysiology, polyamine application The Journal of biological chemistry High 10956662
2003 PKA phosphorylation of GIRK1/GIRK4 channels increases open probability and facilitates activation by Gβγ by reducing dwell time in the long-closed C5 state; the last 20 C-terminal amino acids of GIRK1 are required for PP2A-mediated reduction of apparent Gβγ affinity, identifying this region as part of a phosphorylation-dependent off-switch. Single-channel patch-clamp in isolated Xenopus oocyte membranes, application of PKA catalytic subunit and PP2A, C-terminal truncation mutants Biophysical journal High 12547819
2013 PKA phosphorylation sites on both GIRK1 (S385, S401, T407) and GIRK4 (T199, S412) subunits contribute independently to PKA-mediated facilitation of GIRK1/GIRK4 (IKACh) channels; channels lacking phosphorylatable residues on both subunits show ~97% reduction in PKA-mediated effects. Site-directed mutagenesis of PKA phosphorylation sites, cAMP injection, electrophysiology in Xenopus oocytes, in vitro phosphorylation of truncated cytosolic domains Biochimica et biophysica acta High 23305758
2012 Residues in the GIRK1 pore (P) loop (F137, A142, Y150) collectively potentiate both receptor-dependent and receptor-independent channel activity by enhancing mean open time and single-channel conductance; the distal C-terminal residue Q404 is a key determinant of receptor-induced activity; F162 in TM2 partially opposes the P-loop potentiation. Systematic mutagenesis, single-channel and macroscopic electrophysiology in transfected cells and hippocampal neurons Proceedings of the National Academy of Sciences of the United States of America High 23236146
2000 Gq-coupled m1 muscarinic receptor stimulation suppresses basal and Gi-evoked GIRK1/4 currents via PKC and Ca2+-dependent second messengers; overexpression of Gβγ attenuates this inhibition; the GIRK4 subunit is capable of responding to Gq signals; inhibition does not require phosphorylation of canonical PKC sites on the channel. Electrophysiology in Xenopus oocytes, pharmacological dissection (PKC inhibitors, Ca2+ ionophore, PMA), chimeric channels The Journal of biological chemistry Medium 11060307
2005 PKC-δ mediates inhibition of Kir3.1/3.2 channels following Gq-coupled M3 receptor activation; catalytically active PKC-δ applied to inside-out patches directly inhibits channels; this is reversed by phosphatase; dominant-negative PKC-δ blocks M3-mediated inhibition; GFP-PKC-δ translocates to the plasma membrane after M3 stimulation. Inside-out patch electrophysiology with direct PKC application, dominant-negative overexpression, confocal microscopy, metabolic 32P labeling American journal of physiology. Cell physiology High 15857907
1995 Agonist-induced desensitization of the mu opioid receptor/GIRK1 response in Xenopus oocytes occurs downstream of the receptor (possibly at the channel level), is G protein-independent (GTPγS does not affect rate), and does not involve Ca2+, PKC, or phosphorylation-dependent mechanisms. Two-electrode voltage clamp in Xenopus oocytes, pharmacological dissection (GTPγS, Ca2+ chelators, kinase/phosphatase inhibitors) The Journal of biological chemistry Medium 7822283
1997 The C-terminal peptide DS6 from the very end of GIRK1 directly blocks GIRK channels in inside-out patches (IC50 ~1.7–3.7 μM) by reducing burst duration and increasing long closed times, without competing with Gβγ, suggesting the distal C-terminus is part of the intrinsic gate keeping the channel closed in the absence of Gβγ. Inside-out patch electrophysiology with synthetic peptide application The Journal of physiology Medium 9409468
1996 GIRK1 and CIR (Kir3.4) co-immunoprecipitate from transfected COS cells; GIRK1 localizes to internal cytoskeletal (vimentin-positive) structures alone but traffics to the plasma membrane only when coexpressed with CIR, demonstrating that CIR is required for GIRK1 surface expression. Co-immunoprecipitation, immunofluorescence in COS cells with epitope-tagged subunits Neuropharmacology Medium 8938714
2000 GIRK1 is glycosylated at Asn119 in its extracellular domain; glycosylation at this site does not affect heteromeric channel assembly with GIRK4, surface routing, or IKACh function; GIRK1 transmembrane domain 1 is required for efficient glycosylation at Asn119. Site-directed mutagenesis, glycosidase treatment, immunoblotting, chimeric channel construction in Xenopus oocytes The Journal of biological chemistry Medium 10889209
2019 A gain-of-function missense mutation in KCNJ3 (p.N83H) increases basal IKACh current even in the absence of M2 muscarinic receptor stimulation; transgenic zebrafish expressing this mutant GIRK1 in the atrium develop bradyarrhythmia; the selective IKACh blocker NIP-151 suppresses the increased current and rescues bradyarrhythmia phenotypes. Cellular electrophysiology (gain-of-function characterization), transgenic zebrafish model, pharmacological rescue with NIP-151 Circulation High 30764634
1997 RGS4 co-expression accelerates GIRK1/GIRK2 channel deactivation kinetics and reduces basal current, demonstrating that the GTPase-activating function of RGS proteins controls the temporal gating of GIRK channels by accelerating Gαi GTP hydrolysis. Two-electrode voltage clamp in Xenopus oocytes with RGS4 co-expression, kappa-opioid receptor activation Life sciences Medium 11065178
1999 RGS4 co-expression accelerates deactivation and prevents post-agonist reduction in basal GIRK1/GIRK2 conductance, demonstrating that RGS proteins modulate both the kinetics and steady-state basal activity of GIRK channels. Two-electrode voltage clamp in Xenopus oocytes, kappa-opioid receptor activation Life sciences Medium 10607882
1997 ATP (but not non-hydrolyzable AMP-PNP) applied to inside-out patches restores GIRK1/GIRK4 open probability and open-time distributions to levels seen in cell-attached patches, and this effect is reversed by atrial (but not oocyte) cytosolic extract, suggesting antagonistic modulation by ATP-dependent phosphorylation and an atrial phosphatase underlies rapid desensitization. Inside-out patch electrophysiology in Xenopus oocytes, ATP/cytosolic extract application The American journal of physiology Medium 9038938
2001 Long-term desensitization of IKACh following 24h carbachol exposure in neonatal rat atrial myocytes reduces channel activity at the level of the channel itself (downstream of receptor and G protein), without internalization of the channel, as demonstrated by direct GTPγS and trypsin activation. Cell-attached and inside-out patch electrophysiology, direct G protein and trypsin activation, immunofluorescence for channel localization American journal of physiology. Heart and circulatory physiology Medium 11356610
1996 GIRK1 protein is localized presynaptically in the paraventricular nucleus of the rat hypothalamus, implicating GIRK1/Kir3.1 in presynaptic inhibition of neurotransmitter release by dopamine, noradrenaline, opioids, and histamine. Immunohistochemistry with specific anti-GIRK1 antibody, electron microscopy-level localization Biochemical and biophysical research communications Medium 8645300
1997 GIRK1 protein is found in dendritic spines of CA1 pyramidal cells, often adjacent to asymmetric (excitatory) postsynaptic densities, and in the Golgi of somata, as shown by electron microscopic immunocytochemistry; this localization supports a role for GIRK channels in attenuating excitatory synaptic inputs at the spine level. Electron microscopy immunocytochemistry in rat hippocampus Proceedings of the National Academy of Sciences of the United States of America Medium 9023373
1999 GIRK1 subunit rescues K+ selectivity and G protein dependence of the weaver GIRK2 (G156S) channel when present in an alternating array within a linked tetramer; adjacent mutant subunits cannot be rescued, demonstrating that GIRK1 position within the tetramer determines whether the weaver pore mutation disrupts channel properties. Linked dimer and tetramer constructs expressed in Xenopus oocytes, electrophysiology The Journal of neuroscience High 10493734
1999 GIRK1 channels are activated by reactive oxygen species (superoxide) independently of G protein activation, as shown by hypoxanthine/xanthine oxidase-generated O2•− increasing GIRK1 currents in oocytes; catalase (which removes H2O2) does not block this effect, implicating O2•− directly; Ba2+ fully blocks the current. Two-electrode voltage clamp in Xenopus oocytes expressing GIRK1, ROS-generating system, pharmacological dissection Free radical biology & medicine Medium 9895214
2009 Kir2.1 co-immunoprecipitates with Kir3.1 and Kir3.4 in HEK293T cells, and co-expression of Kir2.1 promotes plasma membrane localization of Kir3.1; a dominant-negative Kir2.1 reduces Kir3.1/3.4 current, indicating inter-subfamily co-assembly. Co-immunoprecipitation, confocal microscopy, dominant-negative electrophysiology in Xenopus oocytes and HEK293T cells Biochemical and biophysical research communications Medium 19338762
2014 In a quantitative model validated in oocytes, HEK293 cells, and hippocampal neurons, 3–4 Gβγ dimers are available per GIRK1/2 channel at all expression levels (consistent with tight Gβγ–GIRK1/2 association), while available Gαi/o per channel decreases with increasing channel density, establishing an unequal stoichiometry of 4 Gβγ and up to 2 Gαi/o per channel. Single-channel and macroscopic electrophysiology, surface density measurements, mathematical modeling, validated in three cell systems PLoS computational biology High 26544551
2013 Nogo receptor 1 (NgR1) siRNA knockdown increases GIRK1 protein levels at the plasma membrane (by cell surface biotinylation) via an mTOR-dependent post-transcriptional mechanism; NgR1 knockout mice show increased GIRK1 in hippocampal synaptosomes, establishing NgR1 as a post-transcriptional regulator of GIRK1 surface expression. siRNA knockdown, cell surface biotinylation, mTOR inhibition, NgR1 knockout mice, synaptosome fractionation Molecular brain Medium 23829864
2020 GAT1508, a urea-based small molecule, selectively activates GIRK1/2 but not GIRK1/4 channels; mutagenesis validated a predicted binding site on GIRK1; computational and experimental evidence shows GAT1508 acts as an allosteric modulator of channel–PIP2 interactions; GAT1508 directly stimulates GIRK currents in basolateral amygdala neurons and facilitates fear extinction in rodents. Chemical screen, electrophysiology, computational modeling, mutagenesis validation, brain-slice electrophysiology, rodent behavioral assay The Journal of biological chemistry High 31953327
2022 Molecular dynamics simulations of GIRK1/2 and GIRK1/4 heterotetramers with activator ML297 and inhibitor GAT1587 identified three hydrophobic TM1 residues of GIRK1 (F87, Y91, W95) that form a hydrophobic wire controlling channel gating; TM2 bending and alignment of acidic GIRK1 residues (E141, D173) in the permeation pathway facilitate K+ conduction; Slide Helix movements control the cytoplasmic gate via CD-loop. Molecular dynamics simulations of heterotetramer models, comparison of activator vs. inhibitor trajectories International journal of molecular sciences Low 36142730

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution. Cell 300 12507423
1995 Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation. Neuron 290 7576656
2007 Crystal structure of a Kir3.1-prokaryotic Kir channel chimera. The EMBO journal 242 17703190
2005 Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification. Nature neuroscience 239 15723059
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
2012 Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in cancer cell metabolism. Proceedings of the National Academy of Sciences of the United States of America 167 22538822
1995 Molecular cloning of a mouse G-protein-activated K+ channel (mGIRK1) and distinct distributions of three GIRK (GIRK1, 2 and 3) mRNAs in mouse brain. Biochemical and biophysical research communications 162 7702616
1996 Cloning of a Xenopus laevis inwardly rectifying K+ channel subunit that permits GIRK1 expression of IKACh currents in oocytes. Neuron 161 8789957
1997 Probing the G-protein regulation of GIRK1 and GIRK4, the two subunits of the KACh channel, using functional homomeric mutants. The Journal of biological chemistry 144 9395492
1995 Activation of inwardly rectifying potassium channels (GIRK1) by co-expressed rat brain cannabinoid receptors in Xenopus oocytes. Neuroscience letters 127 7777206
1996 G-protein-gated inward rectifier K+ channel proteins (GIRK1) are present in the soma and dendrites as well as in nerve terminals of specific neurons in the brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 119 8604043
2006 Heterotrimeric G proteins form stable complexes with adenylyl cyclase and Kir3.1 channels in living cells. Journal of cell science 116 16787947
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
1995 Identification of structural elements involved in G protein gating of the GIRK1 potassium channel. Neuron 115 7576657
1995 Agonist-induced desensitization of the mu opioid receptor-coupled potassium channel (GIRK1). The Journal of biological chemistry 105 7822283
2002 Contribution of the Kir3.1 subunit to the muscarinic-gated atrial potassium channel IKACh. The Journal of biological chemistry 93 12374786
2014 Structural basis for the active site inhibition mechanism of human kidney-type glutaminase (KGA). Scientific reports 91 24451979
2001 Distribution of the muscarinic K+ channel proteins Kir3.1 and Kir3.4 in the ventricle, atrium, and sinoatrial node of heart. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 87 11561006
1995 G beta gamma directly binds to the carboxyl terminus of the G protein-gated muscarinic K+ channel, GIRK1. Biochemical and biophysical research communications 86 7626088
1997 GIRK1 immunoreactivity is present predominantly in dendrites, dendritic spines, and somata in the CA1 region of the hippocampus. Proceedings of the National Academy of Sciences of the United States of America 82 9023373
2019 Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation. Circulation 72 30764634
1997 Coupling of rat somatostatin receptor subtypes to a G-protein gated inwardly rectifying potassium channel (GIRK1). FEBS letters 71 9426226
1997 Opioid receptors from a lower vertebrate (Catostomus commersoni): sequence, pharmacology, coupling to a G-protein-gated inward-rectifying potassium channel (GIRK1), and evolution. Proceedings of the National Academy of Sciences of the United States of America 65 9223341
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
2001 Overexpression of the G-protein inwardly rectifying potassium channel 1 (GIRK1) in primary breast carcinomas correlates with axillary lymph node metastasis. Cancer research 60 11212253
2003 Molecular basis of ion selectivity, block, and rectification of the inward rectifier Kir3.1/Kir3.4 K(+) channel. The Journal of biological chemistry 57 14504281
2000 Inhibition of a Gi-activated potassium channel (GIRK1/4) by the Gq-coupled m1 muscarinic acetylcholine receptor. The Journal of biological chemistry 52 11060307
2004 Coordination of membrane excitability through a GIRK1 signaling complex in the atria. The Journal of biological chemistry 51 15037627
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
1996 Localization and interaction of epitope-tagged GIRK1 and CIR inward rectifier K+ channel subunits. Neuropharmacology 51 8938714
2010 Evidence for oligomerization between GABAB receptors and GIRK channels containing the GIRK1 and GIRK3 subunits. The European journal of neuroscience 48 20846323
2010 NMR analyses of the Gbetagamma binding and conformational rearrangements of the cytoplasmic pore of G protein-activated inwardly rectifying potassium channel 1 (GIRK1). The Journal of biological chemistry 46 21075842
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
2003 Contribution of Kir3.1, Kir3.2A and Kir3.2C subunits to native G protein-gated inwardly rectifying potassium currents in cultured hippocampal neurons. The European journal of neuroscience 45 14622172
1998 Human D2 and D4 dopamine receptors couple through betagamma G-protein subunits to inwardly rectifying K+ channels (GIRK1) in a Xenopus oocyte expression system: selective antagonism by L-741,626 and L-745,870 respectively. Neuropharmacology 45 9833627
2012 Conformational dynamics of Kir3.1/Kir3.2 channel activation via δ-opioid receptors. Molecular pharmacology 43 23175530
1995 Colocalization of mu opioid receptors with GIRK1 potassium channels in the rat brain: an immunocytochemical study. Receptors & channels 43 8821795
2011 Association study of the KCNJ3 gene as a susceptibility candidate for schizophrenia in the Chinese population. Human genetics 42 21927946
2019 Pretreatment with KGA-2727, a selective SGLT1 inhibitor, is protective against myocardial infarction-induced ventricular remodeling and heart failure in mice. Journal of pharmacological sciences 36 31776072
1995 Inhibition of function in Xenopus oocytes of the inwardly rectifying G-protein-activated atrial K channel (GIRK1) by overexpression of a membrane-attached form of the C-terminal tail. Proceedings of the National Academy of Sciences of the United States of America 36 7542774
2010 Gating of a G protein-sensitive mammalian Kir3.1 prokaryotic Kir channel chimera in planar lipid bilayers. The Journal of biological chemistry 34 20937804
2005 PKC-delta sensitizes Kir3.1/3.2 channels to changes in membrane phospholipid levels after M3 receptor activation in HEK-293 cells. American journal of physiology. Cell physiology 34 15857907
1994 G protein-activated inwardly rectifying potassium channel (GIRK1/KGA) mRNA in adult rat heart and brain by in situ hybridization histochemistry. Molecular and cellular neurosciences 34 7704424
1994 Human G-protein-coupled inwardly rectifying potassium channel (GIRK1) gene (KCNJ3): localization to chromosome 2 and identification of a simple tandem repeat polymorphism. Genomics 34 8088798
2006 Blockade by NIP-142, an antiarrhythmic agent, of carbachol-induced atrial action potential shortening and GIRK1/4 channel. Journal of pharmacological sciences 33 16891768
1997 Genomic organization and promoter analysis of the human G-protein-coupled K+ channel Kir3.1 (KCNJ3/HGIRK1). Genomics 30 9119365
1996 G protein-gated K+ channel (GIRK1) protein is expressed presynaptically in the paraventricular nucleus of the hypothalamus. Biochemical and biophysical research communications 29 8645300
2020 The small molecule GAT1508 activates brain-specific GIRK1/2 channel heteromers and facilitates conditioned fear extinction in rodents. The Journal of biological chemistry 28 31953327
2014 Recruitment of Gβγ controls the basal activity of G-protein coupled inwardly rectifying potassium (GIRK) channels: crucial role of distal C terminus of GIRK1. The Journal of physiology 27 25384780
1999 The dual modulation of GIRK1/GIRK2 channels by opioid receptor ligands. European journal of pharmacology 27 10607882
2013 A computational model predicts that Gβγ acts at a cleft between channel subunits to activate GIRK1 channels. Science signaling 26 23943609
2017 Physapubescin, a natural withanolide as a kidney-type glutaminase (KGA) inhibitor. Bioorganic & medicinal chemistry letters 25 28174105
2011 Hesperidin induces antinociceptive effect in mice and its aglycone, hesperetin, binds to μ-opioid receptor and inhibits GIRK1/2 currents. Pharmacology, biochemistry, and behavior 25 21624389
2000 Glycosylation of GIRK1 at Asn119 and ROMK1 at Asn117 has different consequences in potassium channel function. The Journal of biological chemistry 24 10889209
2000 Residues and mechanisms for slow activation and Ba2+ block of the cardiac muscarinic K+ channel, Kir3.1/Kir3.4. The Journal of biological chemistry 24 10956662
2012 Structural elements in the Girk1 subunit that potentiate G protein-gated potassium channel activity. Proceedings of the National Academy of Sciences of the United States of America 22 23236146
2010 Cloning and characterisation of GIRK1 variants resulting from alternative RNA editing of the KCNJ3 gene transcript in a human breast cancer cell line. Journal of cellular biochemistry 22 20512921
1995 Functional expression of an epitope-tagged G protein-coupled K+ channel (GIRK1). The Journal of biological chemistry 22 7540174
2018 GIRK1-mediated inwardly rectifying potassium current suppresses the epileptiform burst activities and the potential antiepileptic effect of ML297. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 29499411
2003 Single channel analysis of the regulation of GIRK1/GIRK4 channels by protein phosphorylation. Biophysical journal 21 12547819
1997 Cloning and characterization of Kir3.1 (GIRK1) C-terminal alternative splice variants. Brain research. Molecular brain research 21 9191093
1997 A C-terminal peptide of the GIRK1 subunit directly blocks the G protein-activated K+ channel (GIRK) expressed in Xenopus oocytes. The Journal of physiology 21 9409468
2003 The selectivity filter may act as the agonist-activated gate in the G protein-activated Kir3.1/Kir3.4 K+ channel. The Journal of biological chemistry 20 14525972
2004 K+ activation of kir3.1/kir3.4 and kv1.4 K+ channels is regulated by extracellular charges. Biophysical journal 19 15454439
2000 Changes in GIRK1/GIRK2 deactivation kinetics and basal activity in the presence and absence of RGS4. Life sciences 19 11065178
2020 Upregulation of GLS1 Isoforms KGA and GAC Facilitates Mitochondrial Metabolism and Cell Proliferation in Epstein-Barr Virus Infected Cells. Viruses 18 32727118
2016 The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 hetero-tetramers. eLife 18 27074664
2015 A Quantitative Model of the GIRK1/2 Channel Reveals That Its Basal and Evoked Activities Are Controlled by Unequal Stoichiometry of Gα and Gβγ. PLoS computational biology 18 26544551
2005 Neuronal Kir3.1/Kir3.2a channels coupled to serotonin 1A and muscarinic m2 receptors are differentially modulated by the "short" RGS3 isoform. Neuropharmacology 18 15935408
1995 Involvement of G-protein alpha il subunits in activation of G-protein gated inward rectifying K+ channels (GIRK1) by human NPY1 receptors. British journal of pharmacology 18 8581266
2019 TNFα increases STAT3-mediated expression of glutaminase isoform KGA in cultured rat astrocytes. Cytokine 16 31344597
2017 Discovery and Characterization of 1H-Pyrazol-5-yl-2-phenylacetamides as Novel, Non-Urea-Containing GIRK1/2 Potassium Channel Activators. ACS chemical neuroscience 16 28697302
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
2016 Overexpression of KCNJ3 gene splice variants affects vital parameters of the malignant breast cancer cell line MCF-7 in an opposing manner. BMC cancer 14 27519272
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
2020 Codon Harmonization of a Kir3.1-KirBac1.3 Chimera for Structural Study Optimization. Biomolecules 13 32164257
2009 Heteromeric assembly of inward rectifier channel subunit Kir2.1 with Kir3.1 and with Kir3.4. Biochemical and biophysical research communications 13 19338762
2000 Kir3.1/3.2 encodes an I(KACh)-like current in gastrointestinal myocytes. American journal of physiology. Gastrointestinal and liver physiology 13 10666054
2010 A real-time screening assay for GIRK1/4 channel blockers. Journal of biomolecular screening 12 20938046
2000 Expression of GIRK (Kir3.1/Kir3.4) channels in mouse fibroblast cells with and without beta1 integrins. FEBS letters 12 10682853
1997 ATP-dependent regulation of a G protein-coupled K+ channel (GIRK1/GIRK4) expressed in oocytes. The American journal of physiology 12 9038938
2021 Analgesic α-conotoxins modulate native and recombinant GIRK1/2 channels via activation of GABAB receptors and reduce neuroexcitability. British journal of pharmacology 11 34599513
2020 Reduced activity of GIRK1-containing heterotetramers is sufficient to affect neuronal functions, including synaptic plasticity and spatial learning and memory. The Journal of physiology 11 33124684
2012 Chronic effects of corticosterone on GIRK1-3 subunits and 5-HT1A receptor expression in rat brain and their reversal by concurrent fluoxetine treatment. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 11 22591911
2001 Cloning and characterization of G protein-gated inward rectifier K+ channel (GIRK1) isoforms from heart and brain. Journal of molecular neuroscience : MN 11 11345517
2014 Prenatal protein malnutrition decreases KCNJ3 and 2DG activity in rat prefrontal cortex. Neuroscience 10 25446346
2001 Evidence of involvement of GIRK1/GIRK4 in long-term desensitization of cardiac muscarinic K+ channels. American journal of physiology. Heart and circulatory physiology 10 11356610
2020 GIRK1-Mediated Inwardly Rectifying Potassium Current Is a Candidate Mechanism Behind Purkinje Cell Excitability, Plasticity, and Neuromodulation. Cerebellum (London, England) 9 32617840
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
2014 Differential effects of genetically-encoded Gβγ scavengers on receptor-activated and basal Kir3.1/Kir3.4 channel current in rat atrial myocytes. Cellular signalling 8 24576551
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
2017 Inhibition of 17-beta-estradiol on neuronal excitability via enhancing GIRK1-mediated inwardly rectifying potassium currents and GIRK1 expression. Journal of the neurological sciences 7 28320163
2013 Molecular basis of the facilitation of the heterooligomeric GIRK1/GIRK4 complex by cAMP dependent protein kinase. Biochimica et biophysica acta 7 23305758
2013 Post-transcriptional regulation of GABAB receptor and GIRK1 channels by Nogo receptor 1. Molecular brain 7 23829864
2006 Base of pore loop is important for rectification, activation, permeation, and block of Kir3.1/Kir3.4. Biophysical journal 7 16513790
2003 Inwardly rectifying Kir3.1 subunit knockdown impairs learning and memory in an olfactory associative task in rat. Brain research. Molecular brain research 7 12750011
2023 Immunoreactivity of Kir3.1, muscarinic receptors 2 and 3 on the brainstem, vagus nerve and heart tissue under experimental demyelination. Brain research bulletin 6 36967090
2022 Use of a Molecular Switch Probe to Activate or Inhibit GIRK1 Heteromers In Silico Reveals a Novel Gating Mechanism. International journal of molecular sciences 6 36142730
2020 A Collision Coupling Model Governs the Activation of Neuronal GIRK1/2 Channels by Muscarinic-2 Receptors. Frontiers in pharmacology 6 32903404
1999 The cardiac acetylcholine-activated, inwardly rectifying K+-channel subunit GIRK1 gives rise to an inward current induced by free oxygen radicals. Free radical biology & medicine 6 9895214