Kir6.1

Description: potassium inwardly-rectifying channel, subfamily J, member 8
Gene: Kcnj8 Synonyms: Kir6.1, kcnj8, sltr, gnite, slmbr

Edit - History

Introduction

KATP channels are present in most, if not all, excitable tissues, and share the property of being inhibited by intracellular nucleotide triphosphates (Ashcroft 1988 [1048]). Structurally unique amongst K channels, these KATP channels are formed by coexpression of an ABC protein (SUR1, or SUR2; Aguilar-Bryan et al., 1995 [1049]; Inagaki et al., 1996 [1050]) and an inward rectifier K channel subunit (Kir6.1 or Kir6.2; Inagaki et al., 1995a [1051], b [1052]; Inagaki et al., 1996 [1050]). Expression of Kir6.2 alone does not result in functional ion channels, suggesting an intimate and requisite interaction between these two subunits. (Shyng [207])

The gene KCNJ8 (also known as KIR6.1; uKATP-1) encodes Kir6.1, an integral membrane protein, inward-rectifier type potassium channel, subfamily J, member 8. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins.

http://www.ncbi.nlm.nih.gov/gene/3764

Edit

Gene

RGD ID	Chromosome	Position	Species
2960	4	180144084-180149935	Rat
10835	6	142513459-142519876	Mouse
731904	12	21917889-21927747	Human

Kcnj8 : potassium inwardly-rectifying channel, subfamily J, member 8

Edit

Transcript

Acc No	Sequence	Length	Source
NM_017099	n/A	n/A	NCBI
NM_008428	n/A	n/A	NCBI
NM_004982	n/A	n/A	NCBI

Edit

Ontology

Accession	Name	Definition	Evidence
GO:0016020	membrane	Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins.	IEA
GO:0008282	ATP-sensitive potassium channel complex	A protein complex that comprises four pore-forming (Kir6.x) and four regulatory sulphonylurea receptor (SURx) subunits and forms a transmembrane channel through which ions may pass. The opening and closing of the channel is regulated by ATP: binding of ATP to the Kir6.2 subunit inhibits channel activity, whereas binding of Mg2+-complexed ATP or ADP to the SUR1 subunit stimulates channel activity.	IDA
GO:0042383	sarcolemma	The outer membrane of a muscle cell, consisting of the plasma membrane, a covering basement membrane (about 100 nm thick and sometimes common to more than one fiber), and the associated loose network of collagen fibers.	IDA
GO:0005792	microsome	Any of the small, heterogeneous, artifactual, vesicular particles, 50-150 nm in diameter, that are formed when some eukaryotic cells are homogenized and that sediment on centrifugation at 100000 g.	IDA
GO:0030016	myofibril	The contractile element of skeletal and cardiac muscle; a long, highly organized bundle of actin, myosin, and other proteins that contracts by a sliding filament mechanism.	IEA
GO:0005739	mitochondrion	A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.	IDA
GO:0016021	integral to membrane	Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane.	IEA

Edit - History

Interaction

KATP channels -of which Kir6.1 is a key unit - are inhibited by increasing intracellular [ATP] and activated by increasing [ADP]. (Ng [1056])

The KATP channel opener diazoxide increased reactive oxygen species production, and glibenclamide abolished this effect. However, in cells lacking Kir6.1 or expressing siRNA or dominant negative constructs of Kir6.1, the same effect was seen. (Ng [1056])

Edit

Protein

Edit

Structure

The KATP channel is an octameric complex comprised of four Kir6.0 subunits from the inward rectifier family of potassium channels and four sulfonylurea receptors (SURs), a member of the ATP- binding cassette family of proteins. The pore-forming sub- unit Kir6.0 has two different members, Kir6.1 and Kir6.2, which share 70% amino acid identity. The regulatory sub- unit SUR is encoded by two distinct genes, SUR1 and SUR2, and is the site of action for antidiabetic drugs such as glibenclamide used in the treatment of type 2 diabetes mellitus (Babenko et al. 1998 [1059]; Seino 1999 [1060]; Rodrigo and Standen 2005 [1041]; Ashcroft and Gribble 1998 [1062]).

Edit - History

Distribution

KATP channels - of which kKr6.1 is a key unit - are present on endomembranes, in particular in mitochondria (‘‘mitoKATP’’) (Inoue et al. 1991 [1057]; Paucek et al. 1992 [1058]).

Cell imaging showed that a major proportion of heterologously expressed Kir6.1-GFP and endogenously expressed Kir6.1 was distributed in the endoplasmic reticulum with little in the mitochondria or plasma membrane. (Ng [1056])

Edit

Expression

Edit - History

Functional

ATP-sensitive potassium (KATP) channels - of which Kir6.1 is a central unit - are involved in a number of physiological and pathophysiological processes and form a link between cellular metabolism and membrane excitability. (Ng [1056])

Kir6.1 plays a role in modifying Ca2+ release from intracellular stores. (Ng [1056])

Edit

Kinetics

Edit

Model

References

207

Shyng S et al. Control of rectification and gating of cloned KATP channels by the Kir6.2 subunit.
J. Gen. Physiol., 1997 Aug , 110 (141-53).

1048

Ashcroft FM Adenosine 5'-triphosphate-sensitive potassium channels.
Annu. Rev. Neurosci., 1988 , 11 (97-118).

1049

Aguilar-Bryan L et al. Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
Science, 1995 Apr 21 , 268 (423-6).

1050

Inagaki N et al. A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.
Neuron, 1996 May , 16 (1011-7).

1051

Inagaki N et al. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
Science, 1995 Nov 17 , 270 (1166-70).

1052

Inagaki N et al. 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., 1995 Mar 17 , 270 (5691-4).

1053

Tester DJ et al. Loss-of-Function Mutations in the KCNJ8-Encoded Kir6.1 KATP Channel and Sudden Infant Death Syndrome.
, 2011 Aug 11 , ().

1054

Medeiros-Domingo A et al. Gain-of-Function Mutation, S422L, in the KCNJ8-Encoded Cardiac K ATP Channel Kir6.1 as a Pathogenic Substrate for J Wave Syndromes.
, 2010 Jun 14 , ().

1055

Chen FR et al. [Effects of Guanxinkang on expressions of ATP-sensitive potassium channel subunits Kir6.1, Kir6.2, SUR2A and SUR2B in ischemic myocytes of rats].
Zhong Xi Yi Jie He Xue Bao, 2010 May , 8 (458-64).

1056

Ng KE et al. The intracellular localization and function of the ATP-sensitive K+ channel subunit Kir6.1.
J. Membr. Biol., 2010 Apr , 234 (137-47).

1057

Inoue I et al. ATP-sensitive K+ channel in the mitochondrial inner membrane.
Nature, 1991 Jul 18 , 352 (244-7).

1058

Paucek P et al. Reconstitution and partial purification of the glibenclamide-sensitive, ATP-dependent K+ channel from rat liver and beef heart mitochondria.
J. Biol. Chem., 1992 Dec 25 , 267 (26062-9).

1059

Babenko AP et al. A view of sur/KIR6.X, KATP channels.
Annu. Rev. Physiol., 1998 , 60 (667-87).

1060

Seino S ATP-sensitive potassium channels: a model of heteromultimeric potassium channel/receptor assemblies.
Annu. Rev. Physiol., 1999 , 61 (337-62).

1061

Rodrigo GC et al. ATP-sensitive potassium channels.
Curr. Pharm. Des., 2005 , 11 (1915-40).

1062

Ashcroft FM et al. Correlating structure and function in ATP-sensitive K+ channels.
Trends Neurosci., 1998 Jul , 21 (288-94).

Edit

Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/ionchannels/53/ , accessed on [date]