Channelpedia

Kir6.2

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

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Introduction

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


Experimental data

Rat Kir6.2 gene in CHO host cells
25 °C
show 29 cells
35 °C
show 20 cells

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Gene

Species NCBI gene ID Chromosome Position
Human 3767 11 4098
Mouse 16514 7 3829
Rat 83535 1 3526

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Transcript

Species NCBI accession Length (nt)
Human NM_000525.4 3412
Mouse NM_010602.3 3115
Rat NM_031358.3 3051

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Protein Isoforms

Species Uniprot ID Length (aa)
Human Q14654 390
Mouse Q61743 390
Rat P70673 390

Isoforms

Transcript
Length (nt)
Protein
Length (aa)
Variant
Isoform

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Post-Translational Modifications

PTM
Position
Type

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Structure

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])

Kir6.2 predicted AlphaFold size

Species Area (Å2) Reference
Human 5299.47 source
Mouse 4619.45 source
Rat 4901.73 source

Methodology for AlphaFold size prediction and disclaimer are available here


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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]).


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Expression and Distribution

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]).


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Function

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]).


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Interaction

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])


References

208

209

496

Coetzee WA et al. Molecular diversity of K+ channels.
Ann. N. Y. Acad. Sci., 1999 Apr 30 , 868 (233-85).

941

Quayle JM et al. ATP-sensitive and inwardly rectifying potassium channels in smooth muscle.
Physiol. Rev., 1997 Oct , 77 (1165-232).

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


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Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/54/ , accessed on 2024 Dec 02



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