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Kir2.3

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Target id: 432

Nomenclature: Kir2.3

Family: Inwardly rectifying potassium channels (KIR)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 1 445 22q13.1 KCNJ4 potassium inwardly rectifying channel subfamily J member 4 15,22,24
Mouse 2 1 445 15 37.74 cM Kcnj4 potassium inwardly-rectifying channel, subfamily J, member 4 11,17
Rat 2 1 446 7q34 Kcnj4 potassium inwardly-rectifying channel, subfamily J, member 4 1-2
Previous and Unofficial Names Click here for help
potassium inwardly rectifying channel subfamily J member 4 | BIR11 | BIRK2 | brain inwardly rectifying K(+) channel 2 | inward rectifier potassium channel 4 | IRK3 | Kcnf2 | MB-IRK3 | potassium channel, inwardly rectifying subfamily J, member 4 | potassium inwardly-rectifying channel | potassium inwardly-rectifying channel, subfamily J, member 4 | potassium voltage-gated channel subfamily J member 4
Database Links Click here for help
Alphafold P48050 (Hs), P52189 (Mm), P52190 (Rn)
CATH/Gene3D 2.60.40.1400
ChEMBL Target CHEMBL2146347 (Hs)
Ensembl Gene ENSG00000168135 (Hs), ENSMUSG00000044216 (Mm), ENSRNOG00000013869 (Rn)
Entrez Gene 3761 (Hs), 16520 (Mm), 116649 (Rn)
Human Protein Atlas ENSG00000168135 (Hs)
KEGG Gene hsa:3761 (Hs), mmu:16520 (Mm), rno:116649 (Rn)
OMIM 600504 (Hs)
Pharos P48050 (Hs)
RefSeq Nucleotide NM_152868 (Hs), NM_008427 (Mm), NM_053870 (Rn)
RefSeq Protein NP_690607 (Hs), NP_032453 (Mm), NP_446322 (Rn)
UniProtKB P48050 (Hs), P52189 (Mm), P52190 (Rn)
Wikipedia KCNJ4 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Kir2.1 20
Kir2.2 20
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
PSD-95 3,7
veli-3 10
CASK 10
SAP97 10
Dp71 10
α-dystrobrevin-2 10
syntrophin 10
chapsyn-110/PSD-93 7
Functional Characteristics Click here for help
IK1 in heart, ‘strong’ inward–rectifier current
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  K+ [13.0 pS]
References:  22
Voltage Dependence Comments
Inactivation and activation of Kir2.3 in Xenopus laevis oocytes are at voltages greater or less than EK respectively (Hs: [15,22,24], Mm: [11,17], Rn: [1-2]).

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
arachidonic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 6.3 pEC50 - -97.0 12
⤷ pEC50 6.3 [12]
Holding voltage: -97.0 mV
tenidap Small molecule or natural product Ligand has a PDB structure Hs Agonist 5.9 – 6.4 pEC50 - -97.0 13
⤷ pEC50 5.9 – 6.4 [13]
Holding voltage: -97.0 mV
Gating inhibitors Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
rose bengal (photoactivated) Small molecule or natural product Mm Antagonist - - 1x10-7 -100.0 – 50.0 6
⤷ Conc range: 1x10-7 M [6]
Holding voltage: -100.0 – 50.0 mV
Extracellular H+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Antagonist 6.7 – 7.4 pKi - -120.0 – -100.0 4,25
⤷ pKi 6.7 – 7.4 [4,25]
Holding voltage: -120.0 – -100.0 mV
Intracellular H+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Antagonist 6.8 – 6.8 pKi - -150.0 – 100.0 23,25
⤷ pKi 6.8 – 6.8 [23,25]
Holding voltage: -150.0 – 100.0 mV
View species-specific gating inhibitor tables
Gating Inhibitor Comments
Endogenous inhibitors are intracellular Mg2+ and polyamines (spermine4+, spermidine3+, putrescine2+).
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
spermine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Antagonist - - 5x10-5 - 1x10-3 -80.0 – 80.0 14
⤷ Conc range: 5x10-5 - 1x10-3 M [14]
Holding voltage: -80.0 – 80.0 mV
putrescine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Hs Antagonist - - 5x10-5 - 1x10-3 -80.0 – 80.0 14
⤷ Conc range: 5x10-5 - 1x10-3 M [14]
Holding voltage: -80.0 – 80.0 mV
spermidine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Hs Antagonist - - 2.5x10-5 - 1x10-3 -80.0 – 80.0 14
⤷ Conc range: 2.5x10-5 - 1x10-3 M [14]
Holding voltage: -80.0 – 80.0 mV
Zn2+ Click here for species-specific activity table Hs Antagonist - - 5x10-5 - 3x10-4 -100.0 – 0.0 4
⤷ Conc range: 5x10-5 - 3x10-4 M [4]
Holding voltage: -100.0 – 0.0 mV
SCH-23390 Small molecule or natural product Click here for species-specific activity table Hs Antagonist - - 1x10-4 -120.0 – 40.0 9
⤷ Conc range: 1x10-4 M [9]
Holding voltage: -120.0 – 40.0 mV
Intracellular Mg2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Antagonist 5.0 pKd - 50.0 14
⤷ pKd 5.0 (Kd 1x10-5 M) [14]
Holding voltage: 50.0 mV
tetraethylammonium Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.2 pKi - 0.0 15
⤷ pKi 4.2 [15]
Holding voltage: 0.0 mV
Cs+ Click here for species-specific activity table Hs Antagonist 1.3 – 4.5 pKi 3x10-6 - 3x10-4 0.0 – -130.0 15
⤷ pKi 1.3 – 4.5 Conc range: 3x10-6 - 3x10-4 M [15]
Holding voltage: 0.0 – -130.0 mV
Ba2+ Click here for species-specific activity table Mm Antagonist 5.2 pIC50 5x10-6 - 5x10-4 -150.0 11,17
⤷ pIC50 5.2 Conc range: 5x10-6 - 5x10-4 M [11,17]
Holding voltage: -150.0 mV
Ba2+ Click here for species-specific activity table Hs Antagonist 5.0 pIC50 3x10-6 - 5x10-4 -60.0 15,20,24
⤷ pIC50 5.0 Conc range: 3x10-6 - 5x10-4 M [15,20,24]
Holding voltage: -60.0 mV
Cs+ Click here for species-specific activity table Mm Antagonist 5.0 pIC50 5x10-6 - 5x10-4 -150.0 11,17
⤷ pIC50 5.0 Conc range: 5x10-6 - 5x10-4 M [11,17]
Holding voltage: -150.0 mV
View species-specific channel blocker tables
Tissue Distribution Click here for help
Heart, hippocampus, amygdala, caudate nucleus, thalamus.
Species:  Human
Technique:  Northern Blot
References:  22
Kidney collecting duct.
Species:  Mouse
Technique:  Immunocytochemistry
References:  18
Reactive astrocytes.
Species:  Rat
Technique:  Immunohistochemistry
References:  19
Postsynaptic membrane at excitatory synapses in the olfactory bulb, neocortex, hippocampus and basal ganglia (caudate putamen).
Also detected in basal forebrain, basal ganglia (nucleus accumbens, globus pallidus), substantia nigra, cerebellum, thalamus.
Species:  Rat
Technique:  Immunohistochemistry
References:  7,21
Cortex (E21+), olfactory bulb (E21+), hippocampus (P1+), striatum (P1+), inferior colliculus (P2-P21), thalamic reticular nucleus (P10+).
Species:  Rat
Technique:  In situ hybridisation
References:  8,21
Schwann cell microvilli.
Species:  Rat
Technique:  Immunocytochemistry
References:  16
Physiological Functions Click here for help
Modulation of cell excitability, modulation of dendritic excitability and plasticity.
Species:  Mouse
Tissue:  Brain
References:  5
Specific distribution at postsynaptic membranes suggests that Kir2.3 participates in maintaining deep resting membrane potential at the postsynaptic region. This is a determinant for the activity of ionotropic glutamate, NMDA- and AMPA-sensitive, receptors.
Species:  Mouse
Tissue:  Brain
References:  7
Physiological Functions Comments
Kir2.3 maintenance of resting membrane potentials.
Although it depends on the species, Kir2.3 in the heart may form channels in complexes with other Kir2 subunits contributing to IK1 [20].

References

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1. Bond CT, Pessia M, Xia XM, Lagrutta A, Kavanaugh MP, Adelman JP. (1994) Cloning and expression of a family of inward rectifier potassium channels. Recept Channels, 2 (3): 183-91. [PMID:7874445]

2. Bredt DS, Wang TL, Cohen NA, Guggino WB, Snyder SH. (1995) Cloning and expression of two brain-specific inwardly rectifying potassium channels. Proc Natl Acad Sci USA, 92 (15): 6753-7. [PMID:7624316]

3. Cohen NA, Brenman JE, Snyder SH, Bredt DS. (1996) Binding of the inward rectifier K+ channel Kir 2.3 to PSD-95 is regulated by protein kinase A phosphorylation. Neuron, 17 (4): 759-67. [PMID:8893032]

4. Coulter KL, Périer F, Radeke CM, Vandenberg CA. (1995) Identification and molecular localization of a pH-sensing domain for the inward rectifier potassium channel HIR. Neuron, 15 (5): 1157-68. [PMID:7576658]

5. Day M, Carr DB, Ulrich S, Ilijic E, Tkatch T, Surmeier DJ. (2005) Dendritic excitability of mouse frontal cortex pyramidal neurons is shaped by the interaction among HCN, Kir2, and Kleak channels. J Neurosci, 25 (38): 8776-87. [PMID:16177047]

6. Duprat F, Guillemare E, Romey G, Fink M, Lesage F, Lazdunski M, Honore E. (1995) Susceptibility of cloned K+ channels to reactive oxygen species. Proc Natl Acad Sci USA, 92 (25): 11796-800. [PMID:8524851]

7. Inanobe A, Fujita A, Ito M, Tomoike H, Inageda K, Kurachi Y. (2002) Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses. Am J Physiol, Cell Physiol, 282 (6): C1396-403. [PMID:11997254]

8. Karschin C, Karschin A. (1997) Ontogeny of gene expression of Kir channel subunits in the rat. Mol Cell Neurosci, 10 (3-4): 131-48. [PMID:9532576]

9. Kuzhikandathil EV, Oxford GS. (2002) Classic D1 dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) directly inhibits G protein-coupled inwardly rectifying potassium channels. Mol Pharmacol, 62 (1): 119-26. [PMID:12065762]

10. Leonoudakis D, Conti LR, Anderson S, Radeke CM, McGuire LM, Adams ME, Froehner SC, Yates 3rd JR, Vandenberg CA. (2004) Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2.x)-associated proteins. J Biol Chem, 279 (21): 22331-46. [PMID:15024025]

11. Lesage F, Duprat F, Fink M, Guillemare E, Coppola T, Lazdunski M, Hugnot JP. (1994) Cloning provides evidence for a family of inward rectifier and G-protein coupled K+ channels in the brain. FEBS Lett, 353 (1): 37-42. [PMID:7926018]

12. Liu Y, Liu D, Heath L, Meyers DM, Krafte DS, Wagoner PK, Silvia CP, Yu W, Curran ME. (2001) Direct activation of an inwardly rectifying potassium channel by arachidonic acid. Mol Pharmacol, 59 (5): 1061-8. [PMID:11306688]

13. Liu Y, Liu D, Printzenhoff D, Coghlan MJ, Harris R, Krafte DS. (2002) Tenidap, a novel anti-inflammatory agent, is an opener of the inwardly rectifying K+ channel hKir2.3. Eur J Pharmacol, 435 (2-3): 153-60. [PMID:11821021]

14. Lopatin AN, Makhina EN, Nichols CG. (1994) Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification. Nature, 372 (6504): 366-9. [PMID:7969496]

15. Makhina EN, Kelly AJ, Lopatin AN, Mercer RW, Nichols CG. (1994) Cloning and expression of a novel human brain inward rectifier potassium channel. J Biol Chem, 269 (32): 20468-74. [PMID:8051145]

16. Mi H, Deerinck TJ, Jones M, Ellisman MH, Schwarz TL. (1996) Inwardly rectifying K+ channels that may participate in K+ buffering are localized in microvilli of Schwann cells. J Neurosci, 16 (8): 2421-9. [PMID:8786419]

17. Morishige K, Takahashi N, Jahangir A, Yamada M, Koyama H, Zanelli JS, Kurachi Y. (1994) Molecular cloning and functional expression of a novel brain-specific inward rectifier potassium channel. FEBS Lett, 346 (2-3): 251-6. [PMID:8013643]

18. Olsen O, Liu H, Wade JB, Merot J, Welling PA. (2002) Basolateral membrane expression of the Kir 2.3 channel is coordinated by PDZ interaction with Lin-7/CASK complex. Am J Physiol, Cell Physiol, 282 (1): C183-95. [PMID:11742811]

19. Perillán PR, Li X, Potts EA, Chen M, Bredt DS, Simard JM. (2000) Inward rectifier K(+) channel Kir2.3 (IRK3) in reactive astrocytes from adult rat brain. Glia, 31 (2): 181-92. [PMID:10878604]

20. Preisig-Müller R, Schlichthörl G, Goerge T, Heinen S, Brüggemann A, Rajan S, Derst C, Veh RW, Daut J. (2002) Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome. Proc Natl Acad Sci USA, 99 (11): 7774-9. [PMID:12032359]

21. Prüss H, Derst C, Lommel R, Veh RW. (2005) Differential distribution of individual subunits of strongly inwardly rectifying potassium channels (Kir2 family) in rat brain. Brain Res Mol Brain Res, 139 (1): 63-79. [PMID:15936845]

22. Périer F, Radeke CM, Vandenberg CA. (1994) Primary structure and characterization of a small-conductance inwardly rectifying potassium channel from human hippocampus. Proc Natl Acad Sci USA, 91 (13): 6240-4. [PMID:8016146]

23. Qu Z, Yang Z, Cui N, Zhu G, Liu C, Xu H, Chanchevalap S, Shen W, Wu J, Li Y et al.. (2000) Gating of inward rectifier K+ channels by proton-mediated interactions of N- and C-terminal domains. J Biol Chem, 275 (41): 31573-80. [PMID:10896660]

24. Tang W, Yang XC. (1994) Cloning a novel human brain inward rectifier potassium channel and its functional expression in Xenopus oocytes. FEBS Lett, 348 (3): 239-43. [PMID:8034048]

25. Zhu G, Chanchevalap S, Cui N, Jiang C. (1999) Effects of intra- and extracellular acidifications on single channel Kir2.3 currents. J Physiol (Lond.), 516 ( Pt 3): 699-710. [PMID:10200419]

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