g protein coupled inwardly rectifying potassium channels

Summary

Summary: A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.

Top Publications

  1. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev. 2010;90:291-366 pubmed publisher
    ..The crystal structure of different Kir channels is opening the way to understanding the structure-function relationships of this simple but diverse ion channel family. ..
  2. Lüscher C, Slesinger P. Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. Nat Rev Neurosci. 2010;11:301-15 pubmed publisher
    ..GIRK channels may therefore prove to be a valuable new therapeutic target. ..
  3. Torrecilla M, Quillinan N, Williams J, Wickman K. Pre- and postsynaptic regulation of locus coeruleus neurons after chronic morphine treatment: a study of GIRK-knockout mice. Eur J Neurosci. 2008;28:618-24 pubmed publisher
  4. Bradaia A, Trube G, Stalder H, Norcross R, Ozmen L, Wettstein J, et al. The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proc Natl Acad Sci U S A. 2009;106:20081-6 pubmed publisher
    ..We hypothesize that the EPPTB-induced increase in the potency of DA at D2 receptors is part of a homeostatic feedback mechanism compensating for the lack of inhibitory TAAR1 tone. ..
  5. Raveh A, Riven I, Reuveny E. Elucidation of the gating of the GIRK channel using a spectroscopic approach. J Physiol. 2009;587:5331-5 pubmed publisher
  6. Aryal P, Dvir H, Choe S, Slesinger P. A discrete alcohol pocket involved in GIRK channel activation. Nat Neurosci. 2009;12:988-95 pubmed publisher
    ..These results provide a tool for developing therapeutic compounds that could mitigate the effects of alcohol. ..
  7. Brevet M, Fucks D, Chatelain D, Regimbeau J, Delcenserie R, Sevestre H, et al. Deregulation of 2 potassium channels in pancreas adenocarcinomas: implication of KV1.3 gene promoter methylation. Pancreas. 2009;38:649-54 pubmed publisher
    ..Methylation of KV1.3 gene promoter could explain the decrease of KV1.3 expression in adenocarcinomas. New therapeutic agents, such as DNA methylation inhibitors, could be useful against this dramatic cancer. ..
  8. Maurice P, Daulat A, Turecek R, Ivankova Susankova K, Zamponi F, Kamal M, et al. Molecular organization and dynamics of the melatonin MT? receptor/RGS20/G(i) protein complex reveal asymmetry of receptor dimers for RGS and G(i) coupling. EMBO J. 2010;29:3646-59 pubmed publisher
  9. Newbury D, Warburton P, Wilson N, Bacchelli E, Carone S, Lamb J, et al. Mapping of partially overlapping de novo deletions across an autism susceptibility region (AUTS5) in two unrelated individuals affected by developmental delays with communication impairment. Am J Med Genet A. 2009;149A:588-97 pubmed publisher
    ..Nevertheless, it remains possible that variants in the flanking genes may underlie evidence of linkage at this locus. ..

More Information

Publications62

  1. Zhang C, Yuan G, Cheng Z, Xu M, Hou L, Wei F. The single nucleotide polymorphisms of Kir3.4 gene and their correlation with lone paroxysmal atrial fibrillation in Chinese Han population. Heart Lung Circ. 2009;18:257-61 pubmed publisher
    ..364 (95% CI 5.710-31.278) and 37.135 (95% CI 9.050-152.381) when comparing patients with T-G genotype. Our findings suggest that C171T and G810T SNPs in Kir3.4 gene might be risk factors for lone paroxysmal AF in Chinese population. ..
  2. González Rodríguez S, Hidalgo A, Baamonde A, Menéndez L. Involvement of Gi/o proteins and GIRK channels in the potentiation of morphine-induced spinal analgesia in acutely inflamed mice. Naunyn Schmiedebergs Arch Pharmacol. 2010;381:59-71 pubmed publisher
  3. Beckstead M, Gantz S, Ford C, Stenzel Poore M, Phillips P, Mark G, et al. CRF enhancement of GIRK channel-mediated transmission in dopamine neurons. Neuropsychopharmacology. 2009;34:1926-35 pubmed publisher
    ..The results indicate that CRF influences dopamine- and GABA-mediated inhibition in the midbrain, suggesting implications for the chronic actions of psychostimulants and stress on dopamine-mediated behaviors. ..
  4. Hommers L, Klenk C, Dees C, Bünemann M. G proteins in reverse mode: receptor-mediated GTP release inhibits G protein and effector function. J Biol Chem. 2010;285:8227-33 pubmed publisher
    ..Consequently, nucleotide-free G proteins were sequestrated in heterotrimeric conformation at the active receptor, thus attenuating downstream signaling in an agonist-dependent manner. ..
  5. Mazarati A, Lundström L, Sollenberg U, Shin D, Langel U, Sankar R. Regulation of kindling epileptogenesis by hippocampal galanin type 1 and type 2 receptors: The effects of subtype-selective agonists and the role of G-protein-mediated signaling. J Pharmacol Exp Ther. 2006;318:700-8 pubmed
    ..The data are important for understanding endogenous mechanisms regulating epileptogenesis and for the development of novel antiepileptogenic drugs. ..
  6. Xie K, Allen K, Kourrich S, Colón Saez J, Thomas M, Wickman K, et al. Gbeta5 recruits R7 RGS proteins to GIRK channels to regulate the timing of neuronal inhibitory signaling. Nat Neurosci. 2010;13:661-3 pubmed publisher
    ..Our findings identify a compartmentalization mechanism that is critical for ensuring high temporal resolution of neuronal G protein signaling. ..
  7. Zhang Z, Rosenhouse Dantsker A, Tang Q, Noskov S, Logothetis D. The RCK2 domain uses a coordination site present in Kir channels to confer sodium sensitivity to Slo2.2 channels. J Neurosci. 2010;30:7554-62 pubmed publisher
    ..The localization of an Na(+) sensor within the RCK2 domain of Slo2.2 further supports the role of RCK (regulators of conductance of K(+)) domains of Slo channels in coupling ion sensing to channel gating. ..
  8. Lujan R, Maylie J, Adelman J. New sites of action for GIRK and SK channels. Nat Rev Neurosci. 2009;10:475-80 pubmed publisher
  9. Cramer N, Best T, Stoffel M, Siarey R, Galdzicki Z. GABAB-GIRK2-mediated signaling in Down syndrome. Adv Pharmacol. 2010;58:397-426 pubmed publisher
  10. Ledonne A, Federici M, Giustizieri M, Pessia M, Imbrici P, Millan M, et al. Trace amines depress D(2)-autoreceptor-mediated responses on midbrain dopaminergic cells. Br J Pharmacol. 2010;160:1509-20 pubmed publisher
  11. Garrison J, Samuel T, Reed J. TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-kappaB. Oncogene. 2009;28:1584-93 pubmed publisher
  12. Ishihara K, Yamamoto T, Kubo Y. Heteromeric assembly of inward rectifier channel subunit Kir2.1 with Kir3.1 and with Kir3.4. Biochem Biophys Res Commun. 2009;380:832-7 pubmed publisher
    ..1 with the wild-type Kir3.1/3.4 decreased the Kir3.1/3.4 current amplitude in Xenopus oocytes. The results indicate that Kir2.1 is capable of forming heteromultimeric channels with Kir3.1 and with Kir3.4. ..
  13. Aron L, Klein P, Pham T, Kramer E, Wurst W, Klein R. Pro-survival role for Parkinson's associated gene DJ-1 revealed in trophically impaired dopaminergic neurons. PLoS Biol. 2010;8:e1000349 pubmed publisher
    ..A better understanding of the molecular connections between trophic signaling, cellular stress and aging could uncover new targets for drug development in PD. ..
  14. Kozell L, Walter N, MILNER L, Wickman K, Buck K. Mapping a barbiturate withdrawal locus to a 0.44 Mb interval and analysis of a novel null mutant identify a role for Kcnj9 (GIRK3) in withdrawal from pentobarbital, zolpidem, and ethanol. J Neurosci. 2009;29:11662-73 pubmed publisher
    ..Thus, our results will be primary to additional efforts to identify genes involved in a wide variety of behavioral responses to sedative-hypnotics and may directly facilitate progress in human genetics. ..
  15. Posokhova E, Wydeven N, Allen K, Wickman K, Martemyanov K. RGS6/G?5 complex accelerates IKACh gating kinetics in atrial myocytes and modulates parasympathetic regulation of heart rate. Circ Res. 2010;107:1350-4 pubmed publisher
    ..Molecular mechanisms regulating this critical signal transduction pathway are not fully understood...
  16. Kawaura K, Honda S, Soeda F, Shirasaki T, Takahama K. [Novel antidepressant-like action of drugs possessing GIRK channel blocking action in rats]. Yakugaku Zasshi. 2010;130:699-705 pubmed
  17. Heusler P, Rauly Lestienne I, Tourette A, Tardif S, Ailhaud M, Croville G, et al. Actions of the prototypical 5-HT1A receptor agonist 8-OH-DPAT at human alpha2-adrenoceptors: (+)8-OH-DPAT, but not (-)8-OH-DPAT is an alpha2B subtype preferential agonist. Eur J Pharmacol. 2010;640:8-14 pubmed publisher
  18. Rusinova R, Shen Y, Dolios G, Padovan J, Yang H, Kirchberger M, et al. Mass spectrometric analysis reveals a functionally important PKA phosphorylation site in a Kir3 channel subunit. Pflugers Arch. 2009;458:303-14 pubmed publisher
    ..Mutation of this residue to alanine resulted in a reduced sensitivity of Kir3.1* currents to H89 and Forskolin, confirming an in vivo role for this novel site of the Kir3.1 channel subunit in its regulation by PKA. ..
  19. Hansen K, Brauner Osborne H. Xenopus oocyte electrophysiology in GPCR drug discovery. Methods Mol Biol. 2009;552:343-57 pubmed publisher
    ..We will focus on the detection of GPCR activation by recordings of currents through CaCCs that are activated by calcium release from the endoplasmic reticulum and thus the G(q) signaling pathway. ..
  20. Ponce Balbuena D, Moreno Galindo E, Lopez Izquierdo A, Ferrer T, Sanchez Chapula J. Tamoxifen inhibits cardiac ATP-sensitive and acetylcholine-activated K+ currents in part by interfering with phosphatidylinositol 4,5-bisphosphate-channel interaction. J Pharmacol Sci. 2010;113:66-75 pubmed
    ..These data suggest that, similar to its effects on Kir2.x currents, tamoxifen inhibits K(ATP) and K(ACh) currents by interfering with the interaction between the channel and PIP(2)...
  21. Stansfeld P, Hopkinson R, Ashcroft F, Sansom M. PIP(2)-binding site in Kir channels: definition by multiscale biomolecular simulations. Biochemistry. 2009;48:10926-33 pubmed publisher
    ..Polar contacts in the coarse-grained simulations corresponded to long-lived electrostatic and H-bonding interactions between the channel and PIP(2) in the atomistic simulations, enabling identification of key side chains. ..
  22. Farhang B, Pietruszewski L, Lutfy K, Wagner E. The role of the NOP receptor in regulating food intake, meal pattern, and the excitability of proopiomelanocortin neurons. Neuropharmacology. 2010;59:190-200 pubmed publisher
    ..Taken together, these results demonstrate the contribution of the NOP receptor in controlling food intake and meal pattern, as well as glutamate release and GIRK1 channel activity at POMC synapses. ..
  23. Schwirtlich M, Emri Z, Antal K, Mate Z, Katarova Z, Szabo G. GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca(2+). FASEB J. 2010;24:1218-28 pubmed publisher
    ..Emri, Z., Antal, K., Máté, Z., Katarova, Z., Szabó, G. GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca(2+). ..
  24. Wang Y, Neubauer F, Lüscher H, Thurley K. GABAB receptor-dependent modulation of network activity in the rat prefrontal cortex in vitro. Eur J Neurosci. 2010;31:1582-94 pubmed publisher
    ..These results show that ambient GABA via GABA(B) receptors is powerful enough to modulate neuronal excitability and the activity of neural networks. ..
  25. Xia Y, Margolis E, Hjelmstad G. Substance P inhibits GABAB receptor signalling in the ventral tegmental area. J Physiol. 2010;588:1541-9 pubmed publisher
  26. Nassirpour R, Bahima L, Lalive A, Lüscher C, Lujan R, Slesinger P. Morphine- and CaMKII-dependent enhancement of GIRK channel signaling in hippocampal neurons. J Neurosci. 2010;30:13419-30 pubmed publisher
    ..These results demonstrate plasticity in neuronal GIRK signaling that may contribute to the abusive effects of morphine...
  27. Xu Y, Shin H, Szep S, Lu Z. Physical determinants of strong voltage sensitivity of K(+) channel block. Nat Struct Mol Biol. 2009;16:1252-8 pubmed publisher
    ..This heretofore unrecognized 'gasket' ensures that the blocker can effectively displace K(+) ions across the selectivity filter to generate exceedingly strong voltage sensitivity. ..
  28. Michaeli A, Yaka R. Dopamine inhibits GABA(A) currents in ventral tegmental area dopamine neurons via activation of presynaptic G-protein coupled inwardly-rectifying potassium channels. Neuroscience. 2010;165:1159-69 pubmed publisher
    ..Accordingly, a novel potential regulatory form of VTA DA neurons' excitability, which involves presynaptic potassium channels, is proposed. ..
  29. Guzman L, Moraga Cid G, Avila A, Figueroa M, Yevenes G, Fuentealba J, et al. Blockade of ethanol-induced potentiation of glycine receptors by a peptide that interferes with Gbetagamma binding. J Pharmacol Exp Ther. 2009;331:933-9 pubmed publisher
  30. Park H, Zhang Y, DU C, Welzig C, Madias C, Aronovitz M, et al. Role of SREBP-1 in the development of parasympathetic dysfunction in the hearts of type 1 diabetic Akita mice. Circ Res. 2009;105:287-94 pubmed publisher
  31. Beckstead M, Phillips T. Mice selectively bred for high- or low-alcohol-induced locomotion exhibit differences in dopamine neuron function. J Pharmacol Exp Ther. 2009;329:342-9 pubmed publisher
  32. Federici M, Nistico R, Giustizieri M, Bernardi G, Mercuri N. Ethanol enhances GABAB-mediated inhibitory postsynaptic transmission on rat midbrain dopaminergic neurons by facilitating GIRK currents. Eur J Neurosci. 2009;29:1369-77 pubmed publisher
    ..These enhancing effects of ethanol on GABA(B)-induced synaptic responses could modulate alcohol intake and the altered mental and motor performance of individuals in an acute intoxicative phase. ..
  33. Wakita S, Izumi Y, Matsuo T, Kume T, Takada Takatori Y, Sawada H, et al. Reconstruction and quantitative evaluation of dopaminergic innervation of striatal neurons in dissociated primary cultures. J Neurosci Methods. 2010;192:83-9 pubmed publisher
    ..By contrast, spinal cells did not increase dopaminergic neurite outgrowth. These results indicate that the present method is valuable for evaluating nigrostriatal projections in vitro. ..
  34. Kleene R, Cassens C, Bähring R, Theis T, Xiao M, Dityatev A, et al. Functional consequences of the interactions among the neural cell adhesion molecule NCAM, the receptor tyrosine kinase TrkB, and the inwardly rectifying K+ channel KIR3.3. J Biol Chem. 2010;285:28968-79 pubmed publisher
    ..Our observations indicate a decisive role for the neuronal K(+) channel in regulating NCAM-dependent neurite outgrowth and attribute a physiologically meaningful role to the functional interplay of Kir3.3, NCAM, and TrkB in ontogeny. ..
  35. Tai K, Stansfeld P, Sansom M. Ion-blocking sites of the Kir2.1 channel revealed by multiscale modeling. Biochemistry. 2009;48:8758-63 pubmed publisher
    ..Interaction sites for spermine are formed by Asp255, Glu299, and Glu224. Entropic factors seem to favor interactions of spermine within the center of the cytoplasmic domain. ..
  36. Raja M, Vales E. Dissimilarity in the channel intrinsic stability among the bacterial KcsA and the inwardly rectifying potassium channel ROMK1. Biochimie. 2009;91:1426-33 pubmed publisher
    ..Our experiments clearly indicate that KcsA and ROMK1 channels differ with regard to their intrinsic stability which might be related to their structural and functional differences. ..
  37. Cavalcanti Kwiatkoski R, Raisman Vozari R, Ginestet L, Del Bel E. Altered expression of neuronal nitric oxide synthase in weaver mutant mice. Brain Res. 2010;1326:40-50 pubmed publisher
    ..Although the functional significance of these changes is not clear, it may represent plastic compensating adjustments resulting from the loss of dopamine innervation, highlighting a possible role of nitric oxide in this process. ..
  38. Kobayashi T, Washiyama K, Ikeda K. Inhibition of G-protein-activated inwardly rectifying K+ channels by the selective norepinephrine reuptake inhibitors atomoxetine and reboxetine. Neuropsychopharmacology. 2010;35:1560-9 pubmed publisher
    ..GIRK channel inhibition may contribute to some of the therapeutic effects of NRIs and adverse side effects related to nervous system and heart function. ..
  39. Berlin S, Keren Raifman T, Castel R, Rubinstein M, Dessauer C, Ivanina T, et al. G alpha(i) and G betagamma jointly regulate the conformations of a G betagamma effector, the neuronal G protein-activated K+ channel (GIRK). J Biol Chem. 2010;285:6179-85 pubmed publisher
    ..Our findings imply that G alpha(i/o) and the G alpha(i) betagamma heterotrimer can regulate a G betagamma effector both before and after activation by neurotransmitters. ..
  40. Andereggen L, Meyer M, Guzman R, Ducray A, Widmer H. Effects of GDNF pretreatment on function and survival of transplanted fetal ventral mesencephalic cells in the 6-OHDA rat model of Parkinson's disease. Brain Res. 2009;1276:39-49 pubmed publisher
    ..In sum, our findings demonstrate that GDNF pretreatment was not disadvantageous for transplants of embryonic rat VM with the FFRT culture technique but only marginally improved graft survival and function. ..
  41. Kurogi M, Nagatomo K, Kubo Y, Saitoh O. Effects of spinophilin on the function of RGS8 regulating signals from M2 and M3-mAChRs. Neuroreport. 2009;20:1134-9 pubmed publisher
    ..Results showed that the recruitment of RGS8 to the receptor differentially affects the function of RGS8 among receptors. ..
  42. Yokogawa M, Muramatsu T, Takeuchi K, Osawa M, Shimada I. Backbone resonance assignments for the cytoplasmic regions of G protein-activated inwardly rectifying potassium channel 1 (GIRK1). Biomol NMR Assign. 2009;3:125-8 pubmed publisher
    ..We established the backbone resonance assignments of (2)H/(13)C/(15)N-labeled cytoplasmic regions of mouse GIRK1, which form a tetramer with a molecular weight of 96 K. ..
  43. Geng X, Du X, Rusinova R, Liu B, Li F, Zhang X, et al. Specificity of Gbetagamma signaling depends on Galpha subunit coupling with G-protein-sensitive K(+) channels. Pharmacology. 2009;84:82-90 pubmed publisher
    ..We present evidence to suggest a key role for the coupling efficiency of Galpha subunits in determining the specificity of Gbetagamma signaling to the channel. ..
  44. Wagner V, Stadelmeyer E, Riederer M, Regitnig P, Gorischek A, DeVaney T, et al. Cloning and characterisation of GIRK1 variants resulting from alternative RNA editing of the KCNJ3 gene transcript in a human breast cancer cell line. J Cell Biochem. 2010;110:598-608 pubmed publisher
    ..The very high abundance of mRNA's encoding GIRK1 together with the presence of GIRK1 protein suggests a pathophysiological role in breast cancer. ..
  45. Chieng B, Christie M. Chronic morphine treatment induces functional delta-opioid receptors in amygdala neurons that project to periaqueductal grey. Neuropharmacology. 2009;57:430-7 pubmed publisher
    ..CeA-periaqueductal grey projections form part of the descending antinociceptive and autonomic control systems suggesting an upregulation of functional DOR in antinociception, emotion and anxiety following chronic morphine treatment. ..
  46. Mullner C, Steinecker B, Gorischek A, Schreibmayer W. Identification of the structural determinant responsible for the phosphorylation of G-protein activated potassium channel 1 by cAMP-dependent protein kinase. FEBS J. 2009;276:6218-26 pubmed publisher
    ..The data obtained in the present study provide information about the structural determinants that are responsible for protein kinase A phosphorylation and the regulation of GIRK channels. ..
  47. Lotsch J, Prüss H, Veh R, Doehring A. A KCNJ6 (Kir3.2, GIRK2) gene polymorphism modulates opioid effects on analgesia and addiction but not on pupil size. Pharmacogenet Genomics. 2010;20:291-7 pubmed publisher
    ..The association of the KCNJ6 rs2070995 AA genotype with increased opioid requirements extends from analgesia to opiate substitution therapy. Opioid induced miosis is exempted for molecular histological reasons. ..
  48. Osawa M, Yokogawa M, Muramatsu T, Kimura T, Mase Y, Shimada I. Evidence for the direct interaction of spermine with the inwardly rectifying potassium channel. J Biol Chem. 2009;284:26117-26 pubmed publisher
  49. Ford C, Phillips P, Williams J. The time course of dopamine transmission in the ventral tegmental area. J Neurosci. 2009;29:13344-52 pubmed publisher
    ..Thus, dopamine transmission in the midbrain is more localized then previously proposed. ..
  50. Spiliopoulos K, Fragioudaki K, Giompres P, Kouvelas E, Mitsacos A. Expression of GluR6 kainate receptor subunit in granular layer of weaver mouse cerebellum. J Neural Transm (Vienna). 2009;116:417-22 pubmed publisher
    ..Our results are indicative of either down-regulation of kainate receptors or modulation of their functional characteristics in weaver granule cells. ..
  51. Li Z, Chen Z, Lan X, Ma L, Qu Y, Liu Y, et al. Two novel cSNPs of weaver gene in Chinese indigenous goat and their associations with milk yield. Mol Biol Rep. 2010;37:563-9 pubmed publisher
    ..05). The observation suggested that the allele "AsuII-A" had the positive effects on adjusted milk yield in the second lactation. ..
  52. Fernandez Alacid L, Aguado C, Ciruela F, Martín R, Colon J, Cabañero M, et al. Subcellular compartment-specific molecular diversity of pre- and post-synaptic GABA-activated GIRK channels in Purkinje cells. J Neurochem. 2009;110:1363-76 pubmed publisher
    ..The association of GIRK channels and GABA(B) receptors with excitatory synapses at both post- and pre-synaptic sites indicates their intimate involvement in the modulation of glutamatergic neurotransmission in the cerebellum. ..
  53. Gravati M, Busnelli M, Bulgheroni E, Reversi A, Spaiardi P, Parenti M, et al. Dual modulation of inward rectifier potassium currents in olfactory neuronal cells by promiscuous G protein coupling of the oxytocin receptor. J Neurochem. 2010;114:1424-35 pubmed publisher
    ..The findings suggest that neuronal excitability might be tuned by a single peptide receptor that mediates opposing effects on distinct K+ channels through the promiscuous coupling to different G proteins. ..