TABLE 4

Kir2.3 channels

Channel name Kir2.3
Description Inwardly rectifying potassium channel Kir2.3 subunit
Other names IRK3, HIR, HRK1, BIRK2, BIR11, hIRK2, MB-IRK3, CCD-IRK3, mKir2.3
Molecular information Human (KCNJ4): 445aa, Locus ID: 3761, GenBank: U07364, S72503, NM_152868,1,2,3 PMID: 8016146,1 chr. 22q13.10
Rat (Kcnj4): 446aa, Locus ID: 116649, GenBank: X83580,4 U27582,5 NM_053870, PMID: 7874445,4 chr. 7q34
Mouse (Kcnj4): 445aa, Locus ID: 16520, GenBank: S71382, NM_008427, PMID: 8013643,6,7 chr. 15, 46.7 centimorgans
Guinea pig (Kcnj4): GenBank: AF18787,4 PMID: 112832298
Associated subunits Kir2.1 and Kir2.2 to form heteromeric channel, auxiliary subunit: PSD-95,9 Chapsyn-110/PSD-93,10 syntrophin, α-dystrobrevin-2, Dp71 (dsystrophin protein 71), SAP97, CASK, Veli-311
Functional assays Voltage-clamp
Current IK1 in the heart with other Kir2 subunits; small conductance channel at basolateral membrane of renal cortical correcting duct
Conductance 13pS in 140 mM symmetric K+6
Ion selectivity K+1
Activation Voltages negative to EK6
Inactivation Voltages positive to EK6
Activators Intracellular alkalization (pK = 6.7612), extracellular alkalization (pK = 7.413,14), PIP2, arachidonic acid (EC50 0.4 μM at —100 mV15), tenidap (EC50 0.4—1.3 μM16)
Inhibitors None
Gating inhibitors ATP (Ki = 1.47 mM17), G protein βγ subunits (Ki, not established18), intracellular acidification (pK = 6.7612), extracellular acidification (pK = 7.413,14), reactive oxygen (Ki, not established19), intracellular Mg2+ (Ki, not established20)
Blockers Ba2+ (IC50 to Kir2.3 homomeric channel, 10.3 μM; to Kir2.1/Kir2.3 heteromeric channel, 6.32 μM; to either Kir2.1—Kir2.3 or Kir2.3—Kir2.1 concatemer, 3.39 μM; to either Kir2.2—Kir2.3 or Kir2.3—Kir2.2 concatemer, 1.73 μM; to Kir2.2/Kir2.3 heteromeric channel, 1.94 μM21)
Cs+ (IC50 to Kir2.3 homomeric channel, 30 μM2)
Internal tetraethylammonium ion (Ki = 62 μM2)
Intracellular Mg2+ (Ki, not established), intracellular polyamines (Ki, not established)22
SCH23390; 34% inhibition at 100 μM23
Radioligands None
Channel distribution Forebrain (after embryonic day 2224), olfactory bulb, hippocampus, cortex, basal ganglia, reactive astrocyte,25 microvilli of Schwann cells,26 postsynaptic membrane at excitatory synapse,10 heart (not rodent), kidney
Physiological functions Maintenance of a resting membrane potential, repolarization of cardiac action potential, modulation of cell excitability; specific distribution at postsynaptic membrane suggests that Kir2.3 participates in keeping a deep resting membrane potential at the postsynaptic region, which is a determinant for the activity of ionotropic glutamate receptors and a N-methyl-d-asparate- and α-aminomethylphosphonic acid-sensitive receptor10; although it depends on the species, Kir2.3 in the heart may form channels in complexes with other Kir2 subunits, contributing a small fraction of IK1
Mutations and pathophysiology Not established
Pharmacological significance Not established

  • aa, amino acids; chr., chromosome; SCH23390, R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride.

  • ↵1. Périer F, Radeke CM, and Vandenberg CA (1994) Primary structure and characterization of a small-conductance inwardly rectifying potassium channel from human hippocampus. Proc Natl Acad Sci USA 91:6240-6244

  • ↵2. Makhina EN, Kelly AJ, Lopatin AN, Mercer RW, and Nichols CG (1994) Cloning and expression of a novel human brain inward rectifier potassium channel. J Biol Chem 269:20468-20474

  • ↵3. Tang W and Yang X-C (1994) Cloning a novel human brain inward rectifier potassium channel and its functional expression in Xenopus oocytes. FEBS Lett 348:239-243

  • ↵4. Bond CT, Pessia M, Xia XM, Lagrutta A, Kavanaugh MP, and Adelman JP (1994) Cloning and expression of a family of inward rectifier potassium channels. Receptor Channels 2:183-194

  • ↵5. Bredt DS, Wang TL, Cohen NA, Guggino WB, and Snyder SH (1995) Cloning and expression of two brain-specific inwardly rectifying potassium channels. Proc Natl Acad Sci USA 92: 6753-6757

  • ↵6. Morishige K, Takahashi N, Jahangir A, Yamada M, Koyama H, Zanelli JS, and Kurachi Y (1994) Molecular cloning and functional expression of a novel brain-specific inward rectifier potassium channel. FEBS Lett 346:251-256

  • ↵7. Lesage F, Duprat F, Fink M, Guillemare E, Coppola T, Lazdunski M, and Hugnot JP (1994) Cloning provides evidence for a family of inward rectifier and G-protein coupled K+ channels in the brain. FEBS Lett 353:37-42

  • ↵8. Liu GX, Derst C, Schlichthorl G, Heinen S, Seebohm G, Bruggemann A, Kummer W, Veh RW, Daut J, and Preisig-Muller R (2001) Comparison of cloned Kir2 channels with native inward rectifier K+ channels from guinea-pig cardiomyocytes. J Physiol 531:115-126

  • ↵9. Cohen NA, Brenman JE, Synder SH, and Bredt DS (1996) Binding of the inward rectifier K+ channel Kir2.3 to PSD-95 regulated by protein kinase A phosphorylation. Neuron 17:759-767

  • ↵10. Inanobe A, Fujita A, Ito M, Tomoike H, Inageda K, and Kurachi Y (2002) Inwardly rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses. Am J Physiol Cell Physiol 282:C1396-C1403

  • ↵11. Leonoudakis D, Conti LR, Anderson S, Radeke CM, McGuire LMM, Adams ME, Froehner SC, Yates JR III, and Vandenberg CA (2004) Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2x)-associated proteins. J Biol Chem 279:22331-22346

  • ↵12. Qu Z, Yang Z, Cui N, Zhu G, Liu C, Xu H, Chanchevalap S, Shen W, Wu J, Li Y, et al. (2000) Gating of inward rectifier K+ channels by protein-mediated interactions of N- and C-terminal domains. J Biol Chem 275:31573-31580

  • ↵13. Coulter KL, Périer F, Radeke CM, and Vandenberg CA (1995) Identification and molecular localization of a pH-sensing domain for the inward rectifier potassium channel HIR. Neuron 15: 1157-1168

  • ↵14. Zhu G, Chanchevalap S, Cui N, and Jiang C. (1999) Effects of intra- and extracellular acidifications on single channel Kir2.3 currents. J Physiol 516:699-710

  • ↵15. Liu Y, Liu D, Heath L, Meyers DM, Krafte DS, Wagoner PK, Silvia CP, Yu W and Curran ME. (2001) Direct activation of an inwardly rectifying potassium channel by arachidonic acid. Mol Pharmacol 59:1061-1068

  • ↵16. Liu Y, Liu D, Printzenhoff D, Coghlan MJ, Harris R, and Krafte DS (2002) Tenidap, a novel anti-inflammatory agent, is an opener of the inwardly rectifying K+ channel hKir2.3. Eur J Pharmacol 435:153-160

  • ↵17. Collins A, German MS, Jan YN, Jan LY, and Zhao B (1996) A strong inwardly rectifying K+ channel that is sensitive to ATP. J Neurosci 16:1-9

  • ↵18. Cohen NA, Brenman JE, Snyder SH, and Bredt DS (1996) Binding of the inward rectifier K+ channel Kir 2.3 to PSD-95 is regulated by protein kinase A phosphorylation. Neuron 17:759-767

  • ↵19. Douprat F, Guillemare E, Romey G, Fink M, Lesage F, Lazdunski M, and Honore E (1995) Susceptibility of cloned K+ channels to reactive oxygen species. Proc Natl Acad Sci USA 92:11796-11800

  • ↵20. Chuang H, Jan YN, and Jan LY (1997) Regulation of inward rectifier K+ channel by m1 acetylcholine receptor and intracellular magnesium. Cell 89:1121-1132

  • ↵21. Preisig-Müller R, Schlichthörl G, Goerge T, Heinen S, Brüggemann A, Rajan S, Derst C, Veh RW, and Daut J (2002) Heteromerization of Kir2x potassium channels contributes to the phenotype of Andersen's syndrome. Proc Natl Acad Sci USA 99:7774-7779

  • ↵22. Lopatin AN, Makhina EN, and Nichols CG. (1995) The mechanism of inward rectification of potassium channels: “long-pore plugging” by cytoplasmic polyamines. J Gen Physiol 106:923-955

  • ↵23. Kuzhikandathil EV and Oxford GS (2002) Classic D1 dopamine receptor antagonist R-(+)7-chloro-8-hydroxy-3-methyl-1-phenyl-2345-tetrahydro-1H-3- benzazepine-hydrochloride (SCH23390) directly inhibits G protein-coupled inwardly rectifying potassium channels. Mol Pharmacol 62:119-126

  • ↵24. Karschin C and Karschin A (1997) Ontogeny of gene expression of Kir channel subunits in the rat. Mol Cell Neurosci 10:131-148

  • ↵25. Perillán PR, Li X, Potts EA, Chen M, Bredt DS, and Simard JM (2000) Inwardly rectifying K+ channel Kir2.3 (IRK3) in reactive astrocytes from adult rat brain. Glia 31: 181-192

  • ↵26. Mi H, Deerinck TJ, Jones M, Ellisman MH, and Schwarz TL (1996) Inwardly rectifying K+ channels that may participate in K+ buffering are localized in microvilli of Schwann cells. J Neurosci 16:2421-2429