K<sub>ir</sub>2.3 | Inwardly rectifying potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Kir2.3

Target id: 432

Nomenclature: Kir2.3

Family: Inwardly rectifying potassium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for Kir2.3 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 1 445 22q13.1 KCNJ4 potassium voltage-gated channel subfamily J member 4 15,22,24
Mouse 2 1 445 15 E1 Kcnj4 potassium inwardly-rectifying channel, subfamily J, member 4 11,17
Rat 2 1 446 7q34 Kcnj4 potassium voltage-gated channel subfamily J member 4 1-2
Previous and Unofficial Names
BIR11 | BIRK2 | IRK3 | MB-IRK3 | brain inwardly rectifying K(+) channel 2 | inward rectifier potassium channel 4 | Kcnf2 | potassium inwardly-rectifying channel, subfamily J, member 4 | potassium channel, inwardly rectifying subfamily J, member 4 | potassium inwardly-rectifying channel
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
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
IK1 in heart, ‘strong’ inward–rectifier current
Ion Selectivity and Conductance
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

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
arachidonic acid Hs Agonist 6.3 pEC50 - -97.0 12
pEC50 6.3 [12]
Holding voltage: -97.0 mV
tenidap Hs Agonist 5.9 – 6.4 pEC50 - -97.0 13
pEC50 5.9 – 6.4 [13]
Holding voltage: -97.0 mV
Gating inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
rose bengal (photoactivated) Mm Antagonist - - 1x10-7 -100.0 – 50.0 6
Conc range: 1x10-7 M [6]
Holding voltage: -100.0 – 50.0 mV
Extracellular H+ 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+ 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 Affinity Units Concentration range (M) Holding voltage (mV) Reference
spermine 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 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 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+ 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 Hs Antagonist - - 1x10-4 -120.0 – 40.0 9
Conc range: 1x10-4 M [9]
Holding voltage: -120.0 – 40.0 mV
Intracellular Mg2+ Hs Antagonist 5.0 pKd - 50.0 14
pKd 5.0 (Kd 1x10-5 M) [14]
Holding voltage: 50.0 mV
tetraethylammonium Hs Antagonist 4.2 pKi - 0.0 15
pKi 4.2 [15]
Holding voltage: 0.0 mV
Cs+ 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+ 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+ 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+ 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
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
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. U.S.A., 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. U.S.A., 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 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. U.S.A., 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. U.S.A., 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, Jiang C. (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]

Contributors

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How to cite this page

Paul A. Slesinger, Colin G. Nichols, Lawrence G. Palmer, Henry Sackin, Stephen Tucker, John P. Adelman, David E. Clapham, Hiroshi Hibino, Atsushi Inanobe, Lily Y. Jan, Andreas Karschin, Yoshihiro Kubo, Yoshihisa Kurachi, Michel Lazdunski, Takashi Miki, Wade L. Pearson, Susumu Seino, Carol A. Vandenberg.
Inwardly rectifying potassium channels: Kir2.3. Last modified on 27/02/2018. Accessed on 16/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=432.