Kir2.1 Explained

The K_ir2.1 inward-rectifier potassium channel is a lipid-gated ion channel encoded by the gene.^{[1] [2] [3] [4]}

Clinical significance

A defect in this gene is associated with Andersen-Tawil syndrome.^[5]

A mutation in the KCNJ2 gene has also been shown to cause short QT syndrome.^[6]

In research

In neurogenetics, Kir2.1 is used in Drosophila research to inhibit neurons, as overexpression of this channel will hyperpolarize cells.

In optogenetics, a trafficking sequence from Kir2.1 has been added to halorhodopsin to improve its membrane localization. The resulting protein eNpHR3.0 is used in optogenetic research to inhibit neurons with light.^[7]

Expression of Kir2.1 gene in human HEK293 cells induce a transient outward current, creating a steady membrane potential close to the reversal potential of potassium.^[8]

Interactions

Kir2.1 has been shown to interact with:

• DLG4,^[9]
• Interleukin 16,^[10] and
• TRAK2^[11]

Further reading

• Kubo Y, Adelman JP, Clapham DE, etal . International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels. . Pharmacol. Rev. . 57 . 4 . 509–26 . 2006 . 16382105 . 10.1124/pr.57.4.11 . 11588492 .
• Wood LS, Tsai TD, Lee KS, Vogeli G . Cloning and functional expression of a human gene, hIRK1, encoding the heart inward rectifier K+-channel. . Gene . 163 . 2 . 313–7 . 1995 . 7590287 . 10.1016/0378-1119(95)00244-Z .
• Kubo Y, Baldwin TJ, Jan YN, Jan LY . Primary structure and functional expression of a mouse inward rectifier potassium channel. . Nature . 362 . 6416 . 127–33 . 1993 . 7680768 . 10.1038/362127a0 . 1993Natur.362..127K . 4243856 .
• Raab-Graham KF, Radeke CM, Vandenberg CA . Molecular cloning and expression of a human heart inward rectifier potassium channel. . NeuroReport . 5 . 18 . 2501–5 . 1995 . 7696590 . 10.1097/00001756-199412000-00024 .
• Ashen MD, O'Rourke B, Kluge KA, etal . Inward rectifier K+ channel from human heart and brain: cloning and stable expression in a human cell line. . Am. J. Physiol. . 268 . 1 Pt 2 . H506–11 . 1995 . 7840300 . 10.1152/ajpheart.1995.268.1.H506.
• Tang W, Qin CL, Yang XC . Cloning, localization, and functional expression of a human brain inward rectifier potassium channel (hIRK1). . Recept. Channels . 3 . 3 . 175–83 . 1996 . 8821791 .
• Tare M, Prestwich SA, Gordienko DV, etal . Inwardly rectifying whole cell potassium current in human blood eosinophils . J. Physiol. . 506 . 2. 303–18 . 1998 . 9490857 . 10.1111/j.1469-7793.1998.303bw.x . 2230727 .
• Rae JL, Shepard AR . Inwardly rectifying potassium channels in lens epithelium are from the IRK1 (Kir 2.1) family . Exp. Eye Res. . 66 . 3 . 347–59 . 1998 . 9533862 . 10.1006/exer.1997.0432 .
• Kurschner C, Yuzaki M . Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein . J. Neurosci. . 19 . 18 . 7770–80 . 1999 . 10479680 . 10.1523/JNEUROSCI.19-18-07770.1999. free . 6782450 .
• Tucker SJ, Ashcroft FM . Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2 . J. Biol. Chem. . 274 . 47 . 33393–7 . 1999 . 10559219 . 10.1074/jbc.274.47.33393 . free .
• Nehring RB, Wischmeyer E, Döring F, etal . Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family . J. Neurosci. . 20 . 1 . 156–62 . 2000 . 10627592 . 10.1523/JNEUROSCI.20-01-00156.2000. free . 6774109 .
• Leonoudakis D, Mailliard W, Wingerd K, etal . Inward rectifier potassium channel Kir2.2 is associated with synapse-associated protein SAP97 . J. Cell Sci. . 114 . Pt 5 . 987–98 . 2001 . 10.1242/jcs.114.5.987 . 11181181 . free .
• Derst C, Karschin C, Wischmeyer E, etal . Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits . FEBS Lett. . 491 . 3 . 305–11 . 2001 . 11240146 . 10.1016/S0014-5793(01)02202-5 . 14452157 . 2001FEBSL.491..305D .
• Stockklausner C, Ludwig J, Ruppersberg JP, Klöcker N . A sequence motif responsible for ER export and surface expression of Kir2.0 inward rectifier K(+) channels . FEBS Lett. . 493 . 2–3 . 129–33 . 2001 . 11287009 . 10.1016/S0014-5793(01)02286-4 . 19230587 . free . 2001FEBSL.493..129S .
• Dart C, Leyland ML . Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying potassium channel, Kir2.1 . J. Biol. Chem. . 276 . 23 . 20499–505 . 2001 . 11287423 . 10.1074/jbc.M101425200 . free .
• Plaster NM, Tawil R, Tristani-Firouzi M, etal . Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome . Cell . 105 . 4 . 511–9 . 2001 . 11371347 . 10.1016/S0092-8674(01)00342-7 . 17015195 . free .
• Jeong JS, Lee HJ, Jung JS, etal . Characterization of inwardly rectifying K(+) conductance across the basolateral membrane of rat tracheal epithelia . Biochem. Biophys. Res. Commun. . 288 . 4 . 914–20 . 2001 . 11688996 . 10.1006/bbrc.2001.5831 .
• Giovannardi S, Forlani G, Balestrini M, etal . Modulation of the inward rectifier potassium channel IRK1 by the Ras signaling pathway . J. Biol. Chem. . 277 . 14 . 12158–63 . 2002 . 11809752 . 10.1074/jbc.M110466200 . free .
• Preisig-Müller R, Schlichthörl G, Goerge T, etal . Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome . Proc. Natl. Acad. Sci. U.S.A. . 99 . 11 . 7774–9 . 2002 . 12032359 . 10.1073/pnas.102609499 . 124349 . 2002PNAS...99.7774P . free .
• Ai T, Fujiwara Y, Tsuji K, etal . Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia . Circulation . 105 . 22 . 2592–4 . 2002 . 12045162 . 10.1161/01.CIR.0000019906.35135.A3 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Andersen-Tawil syndrome
• OMIM entries on Anderson-Tawil syndrome

Notes and References

1. Hansen . SB . Lipid agonism: The PIP2 paradigm of ligand-gated ion channels. . Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids . May 2015 . 1851 . 5 . 620–8 . 10.1016/j.bbalip.2015.01.011 . 25633344. 4540326 .
2. Raab-Graham KF, Radeke CM, Vandenberg CA . Molecular cloning and expression of a human heart inward rectifier potassium channel . NeuroReport . 5 . 18 . 2501–5 . 1994 . 7696590 . 10.1097/00001756-199412000-00024 .
3. Derst C, Karschin C, Wischmeyer E, Hirsch JR, Preisig-Müller R, Rajan S, Engel H, Grzeschik K, Daut J, Karschin A . Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits . FEBS Lett. . 491 . 3 . 305–11 . 2001 . 11240146 . 10.1016/S0014-5793(01)02202-5 . 14452157 . 2001FEBSL.491..305D .
4. Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA . International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels . Pharmacol. Rev. . 57 . 4 . 509–26 . 2005 . 16382105 . 10.1124/pr.57.4.11 . 11588492 .
5. Donaldson MR, Yoon G, Fu YH, Ptacek LJ . Andersen-Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity . Ann. Med. . 36 . 92–7 . 2004 . Suppl 1 . 15176430 . 10.1080/17431380410032490 . 7362563 .
6. Priori SG, Pandit SV, Rivolta I, Berenfeld O, Ronchetti E, Dhamoon A, Napolitano C, Anumonwo J, di Barletta MR, Gudapakkam S, Bosi G, Stramba-Badiale M, Jalife J . A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene . Circ. Res. . 96 . 7 . 800–7 . April 2005 . 15761194 . 10.1161/01.RES.0000162101.76263.8c . free .
7. Gradinaru V, Zhang F, Ramakrishnan C, Mattis J, Prakash R, Diester I, Goshen I, Thompson KR, Deisseroth K . Molecular and cellular approaches for diversifying and extending optogenetics . Cell . 141 . 1 . 154–65 . April 2010 . 20303157 . 4160532 . 10.1016/j.cell.2010.02.037 .
8. Zhang. De-Yong. Lau. Chu-Pak. Li. Gui-Rong. 2009-04-01. Human Kir2.1 channel carries a transient outward potassium current with inward rectification. Pflügers Archiv: European Journal of Physiology. 457. 6. 1275–1285. 10.1007/s00424-008-0608-0. 1432-2013. 19002489. 3120804.
9. Nehring RB, Wischmeyer E, Döring F, Veh RW, Sheng M, Karschin A . Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family . J. Neurosci. . 20 . 1 . 156–62 . 2000 . 10627592 . 6774109 . 10.1523/JNEUROSCI.20-01-00156.2000.
10. Kurschner C, Yuzaki M . Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein . J. Neurosci. . 19 . 18 . 7770–80 . 1999 . 10479680 . 6782450 . 10.1523/JNEUROSCI.19-18-07770.1999.
11. Grishin A, Li H, Levitan ES, Zaks-Makhina E . Identification of gamma-aminobutyric acid receptor-interacting factor 1 (TRAK2) as a trafficking factor for the K+ channel Kir2.1 . J. Biol. Chem. . 281 . 40 . 30104–11 . 2006 . 16895905 . 10.1074/jbc.M602439200 . free .