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Kir6.2

potassium inwardly rectifying channel, subfamily J, member 11
Synonyms: Kir6.2 kcnj11 BIR HHF2 PHHI IKATP TNDM3. Symbol: Kcnj11

Introductions


The ATP-sensitive K + (KATP) channels are potassium permeable ion channels regulated by the ratio of intracellular ATP and ADP concentrations. These channels were first discovered in cardiomyocytes and later found in various tissues, such as pancreatic β cells, pituitary tissue, skeletal muscle, brain, and vascular and nonvascular smooth muscle (Babenko et al., 1998a,b; Huang et al., 2006; Wu et al., 2000, 2006). There are differences in the functional, structural and pharmacological properties of various KATP channels in different tissues (Seino, 1999). Structurally, KATP channels are heteromers composed of inwardly rectifying K+ (Kir6.X) subunits and sulphonylurea receptors (SURs) (Babenko et al., 1998a [1059], b [1063]; Seino, 1999 [1060]). The Kir6.X subunits form a pore-forming structure through which K+ ions transverse the membrane, whereas SUR subunits assemble with the former to modulate the channel's function and to confer unique pharmacological properties to the channel complex (Coetzee et al., 1999 [496]; Miki et al., 2002 [1064]).

The gene KCNJ11 (also known as BIR; HHF2; PHHI; IKATP; TNDM3; KIR6.2; MGC133230) encodes Kir6.2, potassium inwardly-rectifying channel, subfamily J, member 11 This integral membrane protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor SUR. Mutations in this gene are a cause of familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM), transient neonatal diabetes mellitus type 3 (TNDM3), and permanent neonatal diabetes mellitus (PNDM). Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.

http://www.ncbi.nlm.nih.gov/gene/3767

Genes


Kcnj11 : potassium inwardly rectifying channel, subfamily J, member 11

RGD ID Chromosome Position Species
69247 1 96614960-96617993 Rat
69099 7 53352532-53355607 Mouse
69098 11 17406795-17410878 Human

Transcripts


Acc No Sequence Length Source
NM_031358 NCBI
NM_010602 NCBI
NM_000525 NCBI
NM_001166290 NCBI

Ontologies


Accession Name Definition Evidence
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: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: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
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: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:0030315 T-tubule Invagination of the plasma membrane of a muscle cell that extends inward from the cell surface around each myofibril. The ends of T-tubules make contact with the sarcoplasmic reticulum membrane. IDA
GO:0005783 endoplasmic reticulum The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). IDA
GO:0005886 plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. IDA
GO:0005886 plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and 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. IEA

Interactions


Pinacidil and dinitrophenol stimulated large and small KATP channels (i.e. those involving Kir6.2 and Kir6.1 respectively) and both were sensitive to be blocked by glibenclamide. (Wu [209])

Proteins


Structures


As octameric proteins KATP channels possess four pore-forming Kir subunits (Kir6.1 or Kir6.2) and four regulatory sulfonylurea receptor subunits (SUR1 or SUR2). The Kir subunit is a typical inwardly rectifying potassium channel, the SUR subunit is structurally a member of the ABC transporter superfamily. (Diehlmann [1066])

Distributions


Expressions


KATP channels present in heart cells consist of the specific combination of Kir6.2 and SUR2A subunits, whereas the other KATP channels contain Kir6.1 and SUR2B subunits in smooth muscle cells (Seino, 1999 [1060]).

Kir6.2 and SUR2A subunits are predominantly present in the sarcolemma of ventricular myocytes, consistent with the Kir6.2/SUR2A-subunit combi- nation in the sarcolemmal KATP channels (Kuniyasu et al., 2003; Singh et al., 2003 [1065]).

Functionals


The ATP-sensitive K+ (KATP) channels are known to provide a functional linkage between the electrical activity of the cell membrane and metabolism. Two types of inwardly rectifying K+ channel subunits (i.e., Kir6.1 and Kir6.2) with which sulfonylurea receptors are associated were reported to constitute the KATP channels. (Wu [209])

KATP channels are inhibited by physiological intracellular ATP and are activated by increasing intracellular ADP/ATP ratio, e.g. as a result of energy depletion, hypoxia or metabolic stress. As a consequence, K+ efflux leads to hyperpolarization of the membrane, protecting the cell from over-excitability and cell death (Miki et al., 2001 [1064]).

Kinetics


The sarcolemmal KATP channels have been classified into two categories of different biophysical properties: large and small conductance (Quayle et al., 1997 [941]). The single channel conductance of the large conductance KATP channels, which are formed by Kir6.2/SURs, is about 55–90 pS under symmetrical 150 mM K+ or similar conditions (Babenko et al., 1998a [1059],b [1063]; Coetzee et al., 1999 [496]).

Models


References


[208 : 9490811]
[209 : 17097686]
[1059 : 9558481]
[1063 : 9831708]
[1060 : 10099692]
[496 : 10414301]
[1064 : 11984590]
[941 : 9354814]
[1065 : 12738227]
[1066 : 21820692]

Credits