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