Nomenclature: Kir6.1

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. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 0 424 12p11.23 KCNJ8 potassium inwardly-rectifying channel, subfamily J, member 8 2
Mouse 2 0 424 6 G2 Kcnj8 potassium inwardly-rectifying channel, subfamily J, member 8 6
Rat 2 0 424 4q44 Kcnj8 potassium inwardly-rectifying channel, subfamily J, member 8 3
Previous and Unofficial Names
Kir6.1
uKATP-1
uKATP-1
UKATP1
inwardly rectifying potassium channel gene, subfamily J-8 (ATP sensitive)
ATP-sensitive inward rectifier potassium channel 8
Inwardly rectifying potassium channel gene subfamily J-8 (ATP sensitive)
inward rectifier K(+) channel Kir6.1
inwardly rectifier K(+) channel Kir6.1
potassium channel, inwardly rectifying subfamily J member 8
potassium inwardly-rectifying channel, subfamily J, member 8
gnite
slmbr
sltr
AI448900
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
SUR2B 6
Other Associated Proteins
Name References
Not determined
Functional Characteristics
ATP-sensitive, inward-rectifier current
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  K+ [33.0 pS]
References:  6
Ion Selectivity and Conductance Comments
This current was recorded in the Kir6.1/SUR2B channel.
Associated subunits (Human)
SUR1, SUR2A, SUR2B
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
ATP Mm Agonist - - 1x10-3 -60.0 6
Conc range: 1x10-3 M [6]
Holding voltage: -60.0 mV
UDP Mm Agonist - - 1x10-3 -60.0 – 60.0 6
Conc range: 1x10-3 M [6]
Holding voltage: -60.0 – 60.0 mV
nicorandil Mm Agonist - - 3x10-4 -60.0 – 60.0 6
Conc range: 3x10-4 M [6]
Holding voltage: -60.0 – 60.0 mV
diazoxide Mm Agonist - - 2x10-4 -60.0 6
Conc range: 2x10-4 M [6]
Holding voltage: -60.0 mV
pinacidil Mm Agonist - - 1x10-4 -100.0 – 60.0 6
Conc range: 1x10-4 M [6]
Holding voltage: -100.0 – 60.0 mV
GDP Mm Agonist - - 1x10-4 -60.0 – 60.0 6
Conc range: 1x10-4 M [6]
Holding voltage: -60.0 – 60.0 mV
GTP Mm Agonist - - 1x10-7 - 1x10-4 -60.0 6
Conc range: 1x10-7 - 1x10-4 M [6]
Holding voltage: -60.0 mV
cromakalim Hs - - - - -
minoxidil Hs - - - - -
View species-specific activator tables
Activator Comments
Nucleoside diphosphates activate Kir6.1 channels coexpressed with SUR2B [6]. ATP activates and inhibits these channels at low (<10-5M) and high (>10-4M) concentrations, respectively [6]. GTP activates and inhibits Kir6.1 channels at low (<10-5M) and high (>10-4M) concentrations respectively, when coexpressed with SUR2B [6].
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
glibenclamide Hs - - - - -
tolbutamide Hs - - - - -
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
ATP Mm Antagonist - - 1x10-3 - 3x10-3 -60.0 6
Conc range: 1x10-3 - 3x10-3 M [6]
Holding voltage: -60.0 mV
GTP Mm Antagonist - - 3x10-6 -60.0 6
Conc range: 3x10-6 M [6]
Holding voltage: -60.0 mV
Gating Inhibitor Comments
ATP at high concentrations (>10-4M inhibits Kir6.1 channels when coexpressed with SUB2B [6]. GTP at high concentrations (>10-4) when coexpressed with SUR2B [6]
Tissue Distribution
Heart, ovary, adrenal grand > skeletal muscle, lung, brain, stomach, colon, testis, thyroid, pancreatic islet cells > kidney, liver, small intestine, pituitary gland.
Species:  Rat
Technique:  Northern Blot
References:  3
Functional Assays
Patch clamp recording of Kir6.1 expressed in conjunction with SUR2B.
Species:  Mouse
Tissue:  HEK293T cells
Response measured:  Current.
References:  6
Physiological Consequences of Altering Gene Expression
Absence of Kir6.1 expression causes increased susceptibility to endotoxemia through decreased cardiac adaptation.
Species:  Mouse
Tissue:  Heart
Technique:  Knockout
References:  4
Absence of Kir6.1 expression leads to abnormal coronary vasodilation modelling human vasospastic (Printzmetal) angina.
Species:  Mouse
Tissue:  Heart
Technique:  Knockout
References:  5
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnj8tm1Sse Kcnj8tm1Sse/Kcnj8tm1Sse
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1100508  MP:0004215 abnormal myocardial fiber physiology PMID: 11984590 
Kcnj8mydy Kcnj8mydy/Kcnj8mydy
involves: C57BL/6J
MGI:1100508  MP:0001658 increased mortality induced by gamma-irradiation PMID: 18026101 
Kcnj8mydy Kcnj8mydy/Kcnj8mydy
involves: C57BL/6J
MGI:1100508  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 18026101 
Kcnj8sltr Kcnj8sltr/Kcnj8sltr
involves: C57BL/6
MGI:1100508  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 18026101 
Kcnj8gnite Kcnj8gnite/Kcnj8gnite
involves: C57BL/6
MGI:1100508  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 18026101 
Kcnj8slmbr Kcnj8slmbr/Kcnj8slmbr
involves: C57BL/6
MGI:1100508  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 18026101 
Kcnj8mydy Kcnj8mydy/Kcnj8mydy
involves: C57BL/6J
MGI:1100508  MP:0008735 increased susceptibility to endotoxin shock PMID: 18026101 
Kcnj8sos Kcnj8sos/Kcnj8sos
C57BL/6J-Kcnj8
MGI:1100508  MP:0008735 increased susceptibility to endotoxin shock
Kcnj8gnite Kcnj8gnite/Kcnj8gnite
C57BL/6
MGI:1100508  MP:0002418 increased susceptibility to viral infection PMID: 16688530 
Kcnj8sltr Kcnj8sltr/Kcnj8sltr
C57BL/6
MGI:1100508  MP:0002418 increased susceptibility to viral infection PMID: 16688530 
Kcnj8slmbr Kcnj8slmbr/Kcnj8slmbr
C57BL/6
MGI:1100508  MP:0002418 increased susceptibility to viral infection PMID: 16688530 
Kcnj8mydy Kcnj8mydy/Kcnj8mydy
involves: C57BL/6J
MGI:1100508  MP:0002418 increased susceptibility to viral infection PMID: 18026101 
Kcnj8tm1Sse Kcnj8tm1Sse/Kcnj8tm1Sse
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1100508  MP:0001636 irregular heartbeat PMID: 11984590 
Kcnj8tm1Sse Kcnj8tm1Sse/Kcnj8tm1Sse
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1100508  MP:0002083 premature death PMID: 11984590 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Brugada syndrome
Orphanet:  130
References:  1
Mutations not determined

REFERENCES

1. Barajas-Martínez H, Hu D, Ferrer T, Onetti CG, Wu Y, Burashnikov E, Boyle M, Surman T, Urrutia J, Veltmann C et al.. (2012) Molecular genetic and functional association of Brugada and early repolarization syndromes with S422L missense mutation in KCNJ8. Heart Rhythm9 (4): 548-55. [PMID:22056721]

2. Inagaki N, Inazawa J, Seino S. (1995) cDNA sequence, gene structure, and chromosomal localization of the human ATP-sensitive potassium channel, uKATP-1, gene (KCNJ8). Genomics30 (1): 102-4. [PMID:8595887]

3. Inagaki N, Tsuura Y, Namba N, Masuda K, Gonoi T, Horie M, Seino Y, Mizuta M, Seino S. (1995) Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J. Biol. Chem.270 (11): 5691-4. [PMID:7890693]

4. Kane GC, Lam CF, O'Cochlain F, Hodgson DM, Reyes S, Liu XK, Miki T, Seino S, Katusic ZS, Terzic A. (2006) Gene knockout of the KCNJ8-encoded Kir6.1 K(ATP) channel imparts fatal susceptibility to endotoxemia. FASEB J.20 (13): 2271-80. [PMID:17077304]

5. Miki T, Suzuki M, Shibasaki T, Uemura H, Sato T, Yamaguchi K, Koseki H, Iwanaga T, Nakaya H, Seino S. (2002) Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1. Nat. Med.8 (5): 466-72. [PMID:11984590]

6. Yamada M, Isomoto S, Matsumoto S, Kondo C, Shindo T, Horio Y, Kurachi Y. (1997) Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channel. J. Physiol. (Lond.)499 ( Pt 3): 715-20. [PMID:9130167]

To cite this database page, please use the following:

John P. Adelman, David E. Clapham, Hiroshi Hibino, Atsushi Inanobe, Lily Y. Jan, Andreas Karschin, Yoshihiro Kubo, Yoshihisa Kurachi, Michel Lazdunski, Takashi Miki, Colin G. Nichols, Wade L. Pearson, Susumu Seino, Carol A. Vandenberg.
Inwardly rectifying potassium channels: Kir6.1. Last modified on 17/03/2014. Accessed on 22/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=441.

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