Kir2.1 channels
| Channel name | Kir2.1 |
| Description | Inwardly rectifying potassium channel Kir2.1 subunit |
| Other names | IRK1 |
| Molecular information | Human (KCNJ2): 427aa, Locus ID: 3759, GenBank: U12507, NM_000891, PMID: 7696590,1 chr. 17q23.1-24.2 |
| Rat (Kcnj2): 427aa, Locus ID: 29712, GenBank: L48490, NM_017296, PMID: 7603835,2 chr. 10q32.1 | |
| Mouse (Kcnj2): 428aa, Locus ID: 16518, GenBank: X73052, NM_008425, PMID: 7680768,3 chr. 11E2, 11, 68.0 centimorgans | |
| Associated subunits | Kir2.2, Kir4.1, PSD-95,4 SAP97,5 AKAP796 |
| Functional assays | Voltage-clamp |
| Current | IK1 in the heart with other Kir2 subunits |
| Conductance | 23pS (in 140 mM K+)3 |
| Ion selectivity | K+3 |
| Activation | Unblocking of polyamines7,8 |
| Inactivation | Not established |
| Activators | Phosphorylation by PKA and ATP hydrolysis,9 PIP210,11 |
| Inhibitors | PKA phosphorylation,12 tyrosine kinase phosphorylation13 |
| Blockers | Cs+, Rb+,14 Ba2+,15 intracellular Mg2+ (IC50 = 17 μM at +40 mV), putrescine (IC50 = 7.5 μM at +40 mV), spermidine (IC50 = 8.0 nM at +40 mV), spermine (IC50 = 0.9 nM at +40 mV)16 |
| Radioligands | None |
| Channel distribution | Forebrain, heart, skeletal muscle, aortic endothelial cells, macrophage cells,3 olfactory tubercle, dentate gyrus granule cells, caudate putamen, nucleus accumbens, superior colliculus, anterior pretectal nucleus, deep mesencephalic nucleus17 |
| Physiological functions | Maintenance of a resting membrane potential, repolarization of cardiac action potential |
| Mutations and pathophysiology | Andersen's syndrome18 |
| Pharmacological significance | Not established |
aa, amino acids; chr., chromosome; PKA, protein kinase A.
↵1. Raab-Graham KF, Radeke CM, and Vandenberg CA (1994) Molecular cloning and expression of a human heart inward rectifier potassium channel. NeuroReport 5:2501-2505
↵2. Wischmeyer E, Lentes KU, and Karschin A (1995) Physiological and molecular characterization of an IRK-type inward rectifier K+ channel in a tumor mast cell line. Pflueg Arch Eur J Physiol 429:809-819
↵3. Kubo Y, Baldwin TJ, Jan YN, and Jan LY (1993) Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature (Lond) 362:127-133
↵4. Nehring RB, Wischmeyer E, Doring F, Veh RW, Sheng M, and Karschin A (2000) Neuronal inwardly rectifying K+ channels differentially couple to PDZ proteins of the PSD-95/SAP90 family. J Neurosci 20:156-162
↵5. Leonoudakis D, Mailliard W, Wingerd K, Clegg D, and Vandenberg C (2001) Inward rectifier potassium channel Kir2.2 is associated with synapse-associated protein SAP97. J Cell Sci 114:987-998
↵6. Dart C and Leyland ML (2001) Targeting of an A-kinase anchoring protein, AKAP79, to an inwardly rectifying potassium channel, Kir2.1. J Biol Chem 276:20499-20505
↵7. Lopatin AN, Makhina EN, and Nichols CG (1994) Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification. Nature (Lond) 372:366-369
↵8. Ishihara K, Hiraoka M, and Ochi R (1996) The tetravalent organic cation spermine causes the gating of the IRK1 channel expressed in murine fibroblast cells. J Physiol 419:297-320
↵9. Fakler B, Brandle U, Glowatzki E, Zenner HP, and Ruppersberg JP (1994) Kir2.1 inward rectifier K+ channels are regulated independently by protein kinases and ATP hydrolysis. Neuron 13:1413-1420
↵10. Huang CL, Feng S, and Hilgemann DW (1998) Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gβγ. Nature (Lond) 391:803-806
↵11. Soom M, Schonherr R, Kubo Y, Kirsch C, Klinger R, and Heinemann SH (2001) Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels. FEBS Lett 490:49-53
↵12. Wischmeyer E and Karschin A (1996) Receptor stimulation causes slow inhibition of IRK1 inwardly rectifying K+ channels by direct protein kinase A-mediated phosphorylation. Proc Natl Acad Sci USA 93:5819-5823
↵13. Wischmeyer E, Doring F, and Karschin A (1998) Acute suppression of inwardly rectifying Kir2.1 channels by direct tyrosine kinase phosphorylation. J Biol Chem 273:34063-34068
↵14. Abrams CJ, Davies NW, Shelton PA, and Stanfield PR (1996) The role of a single aspartate residue in ionic selectivity and block of a murine inward rectifier K+ channel Kir2.1. J Physiol 493:643-649
↵15. Alagem N, Dvir M, and Reuveny E (2001) Mechanism of Ba2+ block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues. J Physiol 534:381-393
↵16. Yang J, Jan YN, and Jan LY (1995) Control of rectification and permeation by residues in two distinct domains in an inward rectifier K+ channel. Neuron 14:1047-1054
↵17. Karschin C, Dissmann E, Stumer W, and Karschin A (1996) IRK(1–3) and GIRK(1–4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain. J Neurosci 16:3559-3570
↵18. Plaster NM, Tawi R, Tristani-Firouzi M, Canun S, Bendahhou S, Tsunoda A, Donaldson MR, Iannaccone ST, Brunt E, Barohn R, et al. (2001) Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 105:511-519