Kir3.1 channels

Channel name Kir3.1
Description G protein-gated, inwardly rectifying potassium channel Kir3.1 subunit
Other names GIRK1, KGA
Molecular information Human (KCNJ3): 501aa, Locus ID: 3760, GenBank: U50964, NM_002239, PMID: 8804710,1 chr. 2q24.1
Rat (Kcnj3): 501aa, Locus ID: 50599, GenBank: Y12259, NM_031610, PMID: 8642402,2 chr. 3
Mouse (Kcnj3): 501aa, Locus ID: 16519, GenBank: L25264, U01071, NM_008426, PMID: 8355805,3 8234283,4 chr. 2c1.1
Associated subunits Kir3.2, Kir3.4, Kir3.5,5 Kir3.1, is not functional by itself (see “Comments”)
Functional assays Voltage-clamp
Current IGIRK
Conductance 43pS (in 140 mM K+ in oocytes3) [see detail in section for Kir3.2 (Table 7)]
Ion selectivity K+
Activation Gβγ subunits6,7,8
Inactivation Voltage- and RGS protein-dependent9
Activators Gβγ subunits (1–50 nM); modified by PIP2, sodium; Kir3.1/Kir3.2 and Kir3.1/Kir3.4 modified by ethanol [see details in section for Kir3.2 (Table 7)]
Inhibitors Gα subunits (by binding Gβγ subunits),10 protein kinase C11,12
Blockers Nonselective: Ba2+, Cs+ [see details in section for Kir3.2 (Table 7)]
Radioligands None
Channel distribution Olfactory bulb (piriform cortex), neocortex (layers 2–6), hippocampus (dentate gyrus granule cells), basal ganglia (habenula), thalamus midbrain (inferior colliculus), cerebellum (granule cell layer), brainstem (pontine nucleus), atrium3,13
Physiological functions Receptor-dependent hyperpolarization of membrane potential
Mutations and pathophysiology Not established
Pharmacological significance Not established
Comments Kir3.1 is not functional by itself; in the heart, the major form is Kir3.1/3.4 heteromultimer14—in the brain, it is Kir3.1/3.215; the functional expression of Kir3.1 alone in Xenopus oocytes is due to the coassembly with the endogenous Xenopus Kir3 subunit (Kir3.5)5
  • aa, amino acids; chr., chromosome.

  • 1. Schoots O, Yue KT, MacDonald JF, Hampson DR, Nobrega JN, Dixon LM, and Van Tol HH (1996) Cloning of a G-protein activated inwardly rectifying potassium channel from human cerebellum. Brain Res Mol Brain Res 39:23-30

  • 2. Karschin C, Dissmann E, Stühmer W, and Karschin A (1996) IRK1–3 and GIRK1–4 inwardly rectifying K+ channels are differentially expressed in the adult and developing rat CNS. J Neurosci 16: 3559-3571

  • 3. Kubo Y, Reuveny E, Slesinger PA, Jan YN, and Jan LY (1993) Primary structure and functional expression of a rat G protein coupled muscarinic potassium channel. Nature (Lond) 364:802-806

  • 4. Dascal N, Schreibmayer W, Lim NF, Wang W, Chavkin C, Dimangno L, Labarca C, Kieffer BL, Gaveriaux-Ruff C, Trollinger D, et al. (1993) Atrial G protein-activated K+ channel: expression cloning and molecular properties. Proc Natl Acad Sci USA 90:10235-10239

  • 5. Hedin KE, Lim NF, and Clapham DE (1996) Cloning of a Xenopus laevis inwardly rectifying K+ channel subunit that permits GIRK1 expression of IKACh currents in oocytes. Neuron 16:423-429

  • 6. Reuveny E, Slesinger PA, Inglese J, Morales JM, Iniguez-Lluhi JA, Lefkowitz RJ, Bourne HR, Jan YN, and Jan LY (1994) Activation of the cloned muscarinic potassium channel by G protein βγ subunits. Nature (Lond) 370:143-146

  • 7. Wickman KD, Iniguez-Lluhl JA, Davenport PA, Taussig R, Krapivinsky GB, Linder ME, Gilman AG, and Clapham DE (1994) Recombinant G-protein βγ-subunits activate the muscarinic-gated atrial potassium channel. Nature (Lond) 368:255-257

  • 8. Kurachi Y (1995) G protein regulation of cardiac muscarinic potassium channel. Am J Physiol 269:C821-C830

  • 9. Saitoh O, Masuho I, Terakawa I, Nomoto S, Asano T, and Kubo Y (2001) Regulator of G protein signaling 8 (RGS8) requires its NH2 terminus for subcellular localization and acute desensitization of G protein-gated K+ channels. J Biol Chem 276:5052-5058

  • 10. Schreibmayer W, Dessauer CW, Vorobiov D, Gilman AG, Lester HA, Davidson N, and Dascal N (1996) Inhibition of an inwardly rectifying K+ channel by G-protein α-subunits. Nature (Lond) 380:624-627

  • 11. Hill JJ and Peralta EG (2001) Inhibition of a Gi-activated potassium channel (GIRK1/4) by the Gq-coupled m1 muscarinic acetylcholine receptor. J Biol Chem 276:5505-5510

  • 12. Mao J, Wang X, Chen F, Wang R, Rojas A, Shi Y, Piao H, and Jiang C (2004) Molecular basis for the inhibition of G protein-coupled inward rectifier K+ channels by protein kinase C. Proc Natl Acad Sci USA 101:1087-1092

  • 13. 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

  • 14. Krapivinsky G, Gordon E, Wickman K, Velimirovic B, Krapivinsky L, and Clapham DE (1995) The G protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K+ channel proteins. Nature (Lond) 374:135-141

  • 15. Lesage F, Guillemare E, Fink M, Duprat F, Heurteaux C, Fosset M, Romey G, Barhanin J, and Lazdunski M (1995) Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels. J Biol Chem 270:28660-28667