K<sub>ir</sub>2.1 | Inwardly rectifying potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Kir2.1

Target id: 430

Nomenclature: Kir2.1

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 Kir2.1 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 1 427 17q23.1-24.2 KCNJ2 potassium voltage-gated channel subfamily J member 2 22
Mouse 2 1 428 11 E2 Kcnj2 potassium inwardly-rectifying channel, subfamily J, member 2 10
Rat 2 1 427 10q32.1 Kcnj2 potassium voltage-gated channel subfamily J member 2 30
Previous and Unofficial Names
IRK1 | RBL-IRK1 | Kcnf1 | potassium channel, inwardly rectifying subfamily J, member 2 | potassium inwardly-rectifying channel
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kir2.x 19,25
Kir4.1 4
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
PSD-93/Chapsyn 110 14
Filamin-A 24
AKAP79 3
Veli-1 or Veli-3 11-12
CASK 11-12
SAP97 11-13
PSD95 17
Functional Characteristics
IK1 in heart, ‘strong’ inward–rectifier current
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  K+ [21.0 pS]
References:  10

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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
PIP2 Mm Agonist - - 1x10-5 - 5x10-5 -30.0 7,23,27
Conc range: 1x10-5 - 5x10-5 M [7,23,27]
Holding voltage: -30.0 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
oleoyl-CoA Mm Antagonist - - 1.8x10-8 - 1x10-5 -135.0 – -100.0 23,26
Conc range: 1.8x10-8 - 1x10-5 M [23,26]
Holding voltage: -135.0 – -100.0 mV
Gating Inhibitor Comments
Gating is also inhibited by PKA and tyrosine kinase phosphorylation [28-29].
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
Rb+ Mm Antagonist - - 1x10-3 - 1x10-2 -130.0 – -50.0 1
Conc range: 1x10-3 - 1x10-2 M [1]
Holding voltage: -130.0 – -50.0 mV
spermine Mm Antagonist 9.1 pKd - 40.0 8,31
pKd 9.1 [8,31]
Holding voltage: 40.0 mV
spermidine Mm Antagonist 8.1 pKd - 40.0 31
pKd 8.1 [31]
Holding voltage: 40.0 mV
putrescine Mm Antagonist 5.1 pKd - 40.0 8,31
pKd 5.1 [8,31]
Holding voltage: 40.0 mV
Intracellular Mg2+ Mm Antagonist 4.8 pKd - 40.0 31
pKd 4.8 (Kd 1.71x10-5 M) [31]
Holding voltage: 40.0 mV
Ba2+ Mm Antagonist 3.9 – 5.6 pKd 1x10-6 - 1x10-4 0.0 – -80.0 2
pKd 3.9 – 5.6 Conc range: 1x10-6 - 1x10-4 M [2]
Holding voltage: 0.0 – -80.0 mV
Cs+ Mm Antagonist 1.3 – 4.0 pKd 3x10-5 - 3x10-4 0.0 – -102.0 1
pKd 1.3 – 4.0 Conc range: 3x10-5 - 3x10-4 M [1]
Holding voltage: 0.0 – -102.0 mV
Channel Blocker Comments
The action of the majority of these molecules is voltage dependant [1-2,31]. Endogenous inhibitors are intracellular Mg2+ and polyamines (spermine4+, spermidine3+, putrescine2+).
Tissue Distribution
Aortic endothelial cells.
Species:  Human
Technique:  Western blotting
References:  5
Forebrain, skeletal muscle, heart, macrophage cells.
Species:  Mouse
Technique:  Northern Blot
References:  10
Olfactory bulb, neocortex, hippocampus (dentate gyrus), basal ganglia (caudate putamen, nucleus accumbens, lateral olfactory tract nucleus), midbrain (superior colliculus, anterior pretectal nucleus, deep mesencephalic nucleus). motorneurons.
Species:  Rat
Technique:  In situ hybridisation
References:  9,21
Schwann cell microvilli
Species:  Rat
Technique:  Immunocytochemistry
References:  16
Tissue Distribution Comments
Expression in the thalamus has been reported by [21], but not by [9].
Physiological Functions
Maintenance of a resting membrane potential.
Species:  None
Tissue: 
References: 
Repolarisation of cardiac action potential.
Species:  None
Tissue:  Heart.
References: 
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB
MGI:104744  MP:0000455 abnormal maxilla morphology PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB
MGI:104744  MP:0001613 abnormal vasodilation PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB
MGI:104744  MP:0009890 cleft secondary palate PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB
MGI:104744  MP:0001575 cyanosis PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB
MGI:104744  MP:0002058 neonatal lethality PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB
MGI:104744  MP:0009888 palatal shelves fail to meet at midline PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB
MGI:104744  MP:0001954 respiratory distress PMID: 10904001 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Andersen-Tawil syndrome
Synonyms: Andersen cardiodysrhythmic periodic paralysis [OMIM: 170390]
Andersen's syndrome
Andersen syndrome
Cardiodysrhythmic potassium-sensitive periodic paralysis [Orphanet: ORPHA37553]
Disease Ontology: DOID:0050434
OMIM: 170390
Orphanet: ORPHA37553
Role: 
Comments: 
References:  15,18
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
In-frame deletion Human 95_98del 513-524del 18
In-frame deletion Human 314_315del 1167-1172del 18
Missense Human D71V 18
Missense Human S136F 18
Missense Human G144S 18
Missense Human R218W/Q 18
Missense Human G300V 18
Missense Human V302M 15
Missense Human E303K 18
Disease:  Atrial fibrillation, familial, 9; ATFB9
Synonyms: Familial atrial fibrillation [Orphanet: ORPHA334] [Disease Ontology: DOID:0050650]
Disease Ontology: DOID:0050650
OMIM: 613980
Orphanet: ORPHA334
Disease:  Short QT syndrome-3; SQT3
Synonyms: Familial short QT syndrome [Orphanet: ORPHA51083]
OMIM: 609622
Orphanet: ORPHA51083
Role: 
Comments: 
References:  6,20

References

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1. Abrams CJ, Davies NW, Shelton PA, Stanfield PR. (1996) The role of a single aspartate residue in ionic selectivity and block of a murine inward rectifier K+ channel Kir2.1. J. Physiol. (Lond.), 493 ( Pt 3): 643-9. [PMID:8799888]

2. Alagem N, Dvir M, Reuveny E. (2001) Mechanism of Ba(2+) block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues. J. Physiol. (Lond.), 534 (Pt. 2): 381-93. [PMID:11454958]

3. Dart C, Leyland ML. (2001) Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying potassium channel, Kir2.1. J. Biol. Chem., 276 (23): 20499-505. [PMID:11287423]

4. Fakler B, Bond CT, Adelman JP, Ruppersberg JP. (1996) Heterooligomeric assembly of inward-rectifier K+ channels from subunits of different subfamilies: Kir2.1 (IRK1) and Kir4.1 (BIR10). Pflugers Arch., 433 (1-2): 77-83. [PMID:9019734]

5. Fang Y, Schram G, Romanenko VG, Shi C, Conti L, Vandenberg CA, Davies PF, Nattel S, Levitan I. (2005) Functional expression of Kir2.x in human aortic endothelial cells: the dominant role of Kir2.2. Am. J. Physiol., Cell Physiol., 289 (5): C1134-44. [PMID:15958527]

6. Hattori T, Makiyama T, Akao M, Ehara E, Ohno S, Iguchi M, Nishio Y, Sasaki K, Itoh H, Yokode M et al.. (2012) A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents. Cardiovasc. Res., 93 (4): 666-73. [PMID:22155372]

7. Huang CL, Feng S, Hilgemann DW. (1998) Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma. Nature, 391 (6669): 803-6. [PMID:9486652]

8. Ishihara K, Hiraoka M, Ochi R. (1996) The tetravalent organic cation spermine causes the gating of the IRK1 channel expressed in murine fibroblast cells. J. Physiol. (Lond.), 491 ( Pt 2): 367-81. [PMID:8866861]

9. Karschin C, Dissmann E, Stühmer W, Karschin A. (1996) IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain. J. Neurosci., 16 (11): 3559-70. [PMID:8642402]

10. Kubo Y, Baldwin TJ, Jan YN, Jan LY. (1993) Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature, 362 (6416): 127-33. [PMID:7680768]

11. 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]

12. Leonoudakis D, Conti LR, Radeke CM, McGuire LM, Vandenberg CA. (2004) A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. J. Biol. Chem., 279 (18): 19051-63. [PMID:14960569]

13. Leonoudakis D, Mailliard W, Wingerd K, Clegg D, Vandenberg C. (2001) Inward rectifier potassium channel Kir2.2 is associated with synapse-associated protein SAP97. J. Cell. Sci., 114 (Pt 5): 987-98. [PMID:11181181]

14. Leyland ML, Dart C. (2004) An alternatively spliced isoform of PSD-93/chapsyn 110 binds to the inwardly rectifying potassium channel, Kir2.1. J. Biol. Chem., 279 (42): 43427-36. [PMID:15304517]

15. Ma D, Tang XD, Rogers TB, Welling PA. (2007) An andersen-Tawil syndrome mutation in Kir2.1 (V302M) alters the G-loop cytoplasmic K+ conduction pathway. J. Biol. Chem., 282 (8): 5781-9. [PMID:17166852]

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. Nehring RB, Wischmeyer E, Döring F, Veh RW, Sheng M, Karschin A. (2000) Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family. J. Neurosci., 20 (1): 156-62. [PMID:10627592]

18. Plaster NM, Tawil R, Tristani-Firouzi M, Canún S, Bendahhou S, Tsunoda A, Donaldson MR, Iannaccone ST, Brunt E, Barohn R, Clark J, Deymeer F, George AL, Fish FA, Hahn A, Nitu A, Ozdemir C, Serdaroglu P, Subramony SH, Wolfe G, Fu YH, Ptácek LJ. (2001) Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell, 105 (4): 511-9. [PMID:11371347]

19. 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]

20. Priori SG, Pandit SV, Rivolta I, Berenfeld O, Ronchetti E, Dhamoon A, Napolitano C, Anumonwo J, di Barletta MR, Gudapakkam S et al.. (2005) A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ. Res., 96 (7): 800-7. [PMID:15761194]

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. Raab-Graham KF, Radeke CM, Vandenberg CA. (1994) Molecular cloning and expression of a human heart inward rectifier potassium channel. Neuroreport, 5 (18): 2501-5. [PMID:7696590]

23. Rapedius M, Soom M, Shumilina E, Schulze D, Schönherr R, Kirsch C, Lang F, Tucker SJ, Baukrowitz T. (2005) Long chain CoA esters as competitive antagonists of phosphatidylinositol 4,5-bisphosphate activation in Kir channels. J. Biol. Chem., 280 (35): 30760-7. [PMID:15980413]

24. Sampson LJ, Leyland ML, Dart C. (2003) Direct interaction between the actin-binding protein filamin-A and the inwardly rectifying potassium channel, Kir2.1. J. Biol. Chem., 278 (43): 41988-97. [PMID:12923176]

25. Schram G, Melnyk P, Pourrier M, Wang Z, Nattel S. (2002) Kir2.4 and Kir2.1 K(+) channel subunits co-assemble: a potential new contributor to inward rectifier current heterogeneity. J. Physiol. (Lond.), 544 (Pt 2): 337-49. [PMID:12381809]

26. Shumilina E, Klöcker N, Korniychuk G, Rapedius M, Lang F, Baukrowitz T. (2006) Cytoplasmic accumulation of long-chain coenzyme A esters activates KATP and inhibits Kir2.1 channels. J. Physiol. (Lond.), 575 (Pt 2): 433-42. [PMID:16777940]

27. Soom M, Schönherr R, Kubo Y, Kirsch C, Klinger R, Heinemann SH. (2001) Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels. FEBS Lett., 490 (1-2): 49-53. [PMID:11172809]

28. Wischmeyer E, Döring F, Karschin A. (1998) Acute suppression of inwardly rectifying Kir2.1 channels by direct tyrosine kinase phosphorylation. J. Biol. Chem., 273 (51): 34063-8. [PMID:9852063]

29. Wischmeyer E, Karschin A. (1996) Receptor stimulation causes slow inhibition of IRK1 inwardly rectifying K+ channels by direct protein kinase A-mediated phosphorylation. Proc. Natl. Acad. Sci. U.S.A., 93 (12): 5819-23. [PMID:8650176]

30. Wischmeyer E, Lentes KU, Karschin A. (1995) Physiological and molecular characterization of an IRK-type inward rectifier K+ channel in a tumour mast cell line. Pflugers Arch., 429 (6): 809-19. [PMID:7603835]

31. Yang J, Jan YN, Jan LY. (1995) Control of rectification and permeation by residues in two distinct domains in an inward rectifier K+ channel. Neuron, 14 (5): 1047-54. [PMID:7748552]

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: Kir2.1. Last modified on 27/02/2018. Accessed on 18/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=430.