Inward-rectifier potassium channel: Difference between revisions

'''Inward-rectifier potassium channels''' ('''K_ir''', '''IRK''') are a specific [[Lipid-gated_ion_channels|lipid-gated]] subset of [[potassium channel]]s. To date, seven subfamilies have been identified in various mammalian cell types,<ref name="Kubo">{{cite journal | vauthors = Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA | display-authors = 6 | title = International Union of Pharmacology. LIV. Nomenclature and Molecular Relationships of Inwardly Rectifying Potassium Channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 509–26 | date = December 2005 | pmid = 16382105 | doi = 10.1124/pr.57.4.11 | s2cid = 11588492 | authorlink8 = Colin Nichols }}</ref> plants,<ref name="pmid8582318">{{cite journal | vauthors = Hedrich R, Moran O, Conti F, Busch H, Becker D, Gambale F, Dreyer I, Küch A, Neuwinger K, Palme K | display-authors = 6 | title = Inward rectifier potassium channels in plants differ from their animal counterparts in response to voltage and channel modulators | journal = European Biophysics Journal | volume = 24 | issue = 2 | pages = 107–15 | year = 1995 | pmid = 8582318 | doi = 10.1007/BF00211406 | s2cid = 12718513 }}</ref> and bacteria.<ref name="tcdb.org">{{Cite web|url = http://www.tcdb.org/search/result.php?tc=1.A.2|title = 1.A.2 Inward Rectifier K Channel (IRK-C) Family|website = TCDB|access-date = 2016-04-09}}</ref> They are activated by phosphatidylinositol 4,5-bisphosphate ([[Phosphatidylinositol 4,5-bisphosphate|PIP₂]]). The malfunction of the channels has been implicated in several diseases.<ref>{{cite journal | vauthors = Hansen SB | title = Lipid agonism: The PIP2 paradigm of ligand-gated ion channels | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1851 | issue = 5 | pages = 620–8 | date = May 2015 | pmid = 25633344 | pmc = 4540326 | doi = 10.1016/j.bbalip.2015.01.011 }}</ref><ref name="Abraham">{{cite journal | vauthors = Abraham MR, Jahangir A, Alekseev AE, Terzic A | title = Channelopathies of inwardly rectifying potassium channels | journal = FASEB Journal | volume = 13 | issue = 14 | pages = 1901–10 | date = November 1999 | pmid = 10544173 | doi = 10.1096/fasebj.13.14.1901 | s2cid = 22205168 }}</ref> IRK channels possess a pore domain, homologous to that of [[voltage-gated ion channel]]s, and flanking [[transmembrane domain|transmembrane segments]] (TMSs). They may exist in the membrane as homo- or heterooligomers and each monomer possesses between 2 and 4 TMSs. In terms of function, these proteins transport [[potassium|potassium (K⁺)]], with a greater tendency for K⁺ uptake than K⁺ export.<ref name="tcdb.org"/> The process of inward-rectification was discovered by [[Denis Noble]] in cardiac muscle cells in 1960s and by [[Richard Adrian, 2nd Baron Adrian|Richard Adrian]] and [[Alan Lloyd Hodgkin|Alan Hodgkin]] in 1970 in skeletal muscle cells.<ref>{{cite journal | vauthors = Adrian RH, Chandler WK, Hodgkin AL | title = Slow changes in potassium permeability in skeletal muscle | journal = The Journal of Physiology | volume = 208 | issue = 3 | pages = 645–68 | date = July 1970 | pmid = 5499788 | pmc = 1348790 | doi = 10.1113/jphysiol.1970.sp009140 }}</ref>

| [[neurons]] and in heart cells || [[G protein-coupled inwardly-rectifying potassium channel|G-protein activated IRKs (K_ir3)]] are important regulators, modulated by neurotransmitters. A mutation in the [[KCNJ6|GIRK2]] channel leads to the weaver mouse mutation. "Weaver" mutant mice are ataxic and display a neuroinflammation-mediated degeneration of their dopaminergic neurons.<ref>{{cite journal | vauthors = Peng J, Xie L, Stevenson FF, Melov S, Di Monte DA, Andersen JK | title = Nigrostriatal dopaminergic neurodegeneration in the weaver mouse is mediated via neuroinflammation and alleviated by minocycline administration | journal = The Journal of Neuroscience | volume = 26 | issue = 45 | pages = 11644–51 | date = November 2006 | pmid = 17093086 | pmc = 6674792 | doi = 10.1523/JNEUROSCI.3447-06.2006 }}</ref> Relative to non-ataxic controls, Weaver mutants have deficits in motor coordination and changes in regional brain metabolism.<ref>{{cite journal | vauthors = Strazielle C, Deiss V, Naudon L, Raisman-Vozari R, Lalonde R | title = Regional brain variations of cytochrome oxidase activity and motor coordination in Girk2(Wv) (Weaver) mutant mice | journal = Neuroscience | volume = 142 | issue = 2 | pages = 437–49 | date = October 2006 | pmid = 16844307 | doi = 10.1016/j.neuroscience.2006.06.011 | s2cid = 33064439 }}</ref> Weaver mice have been examined in labs interested in neural development and disease for over 30 years.

The crystal structure<ref>{{cite journal | vauthors = Kuo A, Gulbis JM, Antcliff JF, Rahman T, Lowe ED, Zimmer J, Cuthbertson J, Ashcroft FM, Ezaki T, Doyle DA | display-authors = 6 | title = Crystal structure of the potassium channel KirBac1.1 in the closed state | journal = Science | volume = 300 | issue = 5627 | pages = 1922–6 | date = June 2003 | pmid = 12738871 | doi = 10.1126/science.1085028 | bibcode = 2003Sci...300.1922K | s2cid = 2703162 }}</ref> and function<ref name=":0">{{cite journal | vauthors = Enkvetchakul D, Bhattacharyya J, Jeliazkova I, Groesbeck DK, Cukras CA, Nichols CG | title = Functional characterization of a prokaryotic Kir channel | journal = The Journal of Biological Chemistry | volume = 279 | issue = 45 | pages = 47076–80 | date = November 2004 | pmid = 15448150 | doi = 10.1074/jbc.C400417200 | doi-access = free }}</ref> of bacterial members of the IRK-C family have been determined. KirBac1.1, from ''[[Burkholderia pseudomallei]]'', is 333 amino acyl residues (aas) long with two N-terminal TMSs flanking a P-loop (residues 1-150), and the C-terminal half of the protein is hydrophilic. It transports monovalent cations with the selectivity: K ≈ Rb ≈ Cs ≫ Li ≈ Na ≈ NMGM (protonated [[N-methyl-D-glucamine]]). Activity is inhibited by Ba²⁺, Ca²⁺, and low pH.<ref name=":0" />