Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2.
paper
Cited
Public
Unavailable
- Authors
- Signorini, S; Liao, Y J; Duncan, S A; Jan, L Y; Stoffel, M
- Year
- 1997
- Journal
- Proceedings of the National Academy of Sciences of the United States of America
- PMID
- 9023358
- DOI
- 10.1073/pnas.94.3.923
- PMCID
- PMC19615
G protein-gated, inwardly rectifying K+ channels (GIRK) are effectors of G protein-coupled receptors for neurotransmitters and hormones and may play an important role in the regulation of neuronal excitability. GIRK channels may be important in neurodevelopment, as suggested by the recent finding that a point mutation in the pore region of GIRK2 (G156S) is responsible for the weaver (wv) phenotype. The GIRK2 G156S gene gives rise to channels that exhibit a loss of K+ selectivity and may also exert dominant-negative effects on G(betagamma)-activated K+ currents. To investigate the physiological role of GIRK2, we generated mutant mice lacking GIRK2. Unlike wv/wv mutant mice, GIRK2 -/- mice are morphologically indistinguishable from wild-type mice, suggesting that the wv phenotype is likely due to abnormal GIRK2 function. Like wv/wv mice, GIRK2 -/- mice have much reduced GIRK1 expression in the brain. They also develop spontaneous seizures and are more susceptible to pharmacologically induced seizures using a gamma-aminobutyric acid antagonist. Moreover, wv/- mice exhibit much milder cerebellar abnormalities than wv/wv mice, indicating a dosage effect of the GIRK2 G156S mutation. Our results indicate that the weaver phenotypes arise from a gain-of-function mutation of GIRK2 and that GIRK1 and GIRK2 are important mediators of neuronal excitability in vivo.
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| Inhibition of G-protein-coupled inward rectifying K+ channels by intracellular acidosis. | Mao J et al. | β | 2003 | β |
| Inwardly rectifying Kir3.1 subunit knockdown impairs learning and memory in an olfactory associative task in rat. | Kourrich S et al. | β | 2003 | β |
| Kir channels in the CNS: emerging new roles and implications for neurological diseases. | Neusch C et al. | β | 2003 | β |
| Molecular biology and ontogeny of gamma-aminobutyric acid (GABA) receptors in the mammalian central nervous system. | Simeone TA et al. | β | 2003 | β |
| Mutation of KCNK5 or Kir3.2 potassium channels in mice does not change minimum alveolar anesthetic concentration. | Gerstin KM et al. | β | 2003 | β |
| Reduced ethanol-induced conditioned taste aversion and conditioned place preference in GIRK2 null mutant mice. | Hill KG et al. | β | 2003 | β |
| Suppression of epileptiform activity by GABA(B) receptors in wild type and weaver hippocampus 'in vitro'. | Yanovsky Y et al. | β | 2003 | β |
| Cell death in weaver mouse cerebellum. | Harkins AB et al. | β | 2002 | β |
| Critical role for GALR1 galanin receptor in galanin regulation of neuroendocrine function and seizure activity. | Jacoby AS et al. | β | 2002 | β |
| Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from brain and heart. | Ma D et al. | β | 2002 | β |
| G-protein-gated potassium channels containing Kir3.2 and Kir3.3 subunits mediate the acute inhibitory effects of opioids on locus ceruleus neurons. | Torrecilla M et al. | β | 2002 | β |
| Hyperalgesia and blunted morphine analgesia in G protein-gated potassium channel subunit knockout mice. | Marker CL et al. | β | 2002 | β |
| K(+) channels as therapeutic drug targets. | Wickenden A | β | 2002 | β |
| Molecular mechanisms of analgesia induced by opioids and ethanol: is the GIRK channel one of the keys? | Ikeda K et al. | β | 2002 | β |
| Neocortical potassium currents are enhanced by the antiepileptic drug lamotrigine. | Zona C et al. | β | 2002 | β |
| Potassium channel mRNAs with AU-rich elements and brain-specific expression. | Suda S et al. | β | 2002 | β |
| Potassium channels as anti-epileptic drug targets. | Wickenden AD | β | 2002 | β |
| Suggestive evidence for association of two potassium channel genes with different idiopathic generalised epilepsy syndromes. | Chioza B et al. | β | 2002 | β |
| A novel gene causing a mendelian audiogenic mouse epilepsy. | Skradski SL et al. | β | 2001 | β |
| Confirmation of the retinopetal/centrifugal nature of the tyrosine hydroxylase-immunoreactive fibers of the retina and optic nerve in the weaver mouse. | Simon A et al. | β | 2001 | β |
| Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice. | Prosser HM et al. | β | 2001 | β |
| Generalized epileptic disorders: an update. | Avoli M et al. | β | 2001 | β |
| GIRK2 deficient mice. Evidence for hyperactivity and reduced anxiety. | Blednov YA et al. | β | 2001 | β |
| Ion selectivity filter regulates local anesthetic inhibition of G-protein-gated inwardly rectifying K+ channels. | Slesinger PA | β | 2001 | β |
| Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. | Neusch C et al. | β | 2001 | β |
| Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption. | BΓΆsl MR et al. | β | 2001 | β |
| Mechanism underlying bupivacaine inhibition of G protein-gated inwardly rectifying K+ channels. | Zhou W et al. | β | 2001 | β |
| The Stoichiometry of Gbeta gamma binding to G-protein-regulated inwardly rectifying K+ channels (GIRKs). | Corey S et al. | β | 2001 | β |
| Antisense suppression of potassium channel expression demonstrates its role in maturation of the action potential. | Vincent A et al. | β | 2000 | β |
| Are some idiopathic epilepsies disorders of ion channels?: A working hypothesis. | Hirose S et al. | β | 2000 | β |
| Dominant-negative mutants identify a role for GIRK channels in D3 dopamine receptor-mediated regulation of spontaneous secretory activity. | Kuzhikandathil EV et al. | β | 2000 | β |
| Dysfunctions in mice by NMDA receptor point mutations NR1(N598Q) and NR1(N598R). | Single FN et al. | β | 2000 | β |
| Evidence of elevated intracellular calcium levels in weaver homozygote mice. | Harkins AB et al. | β | 2000 | β |
| Gain of function mutants: ion channels and G protein-coupled receptors. | Lester HA et al. | β | 2000 | β |
| G-protein mediated gating of inward-rectifier K+ channels. | Mark MD et al. | β | 2000 | β |
| Impaired fast-spiking, suppressed cortical inhibition, and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins. | Lau D et al. | β | 2000 | β |
| Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes. | Kobayashi T et al. | β | 2000 | β |
| Insights from mouse models into the molecular basis of neurodegeneration. | Heintz N et al. | β | 2000 | β |
| Involvement of GIRK2 in postnatal development of the weaver cerebellum. | Liesi P et al. | β | 2000 | β |
| KCNQ2/KCNQ3 K+ channels and the molecular pathogenesis of epilepsy: implications for therapy. | Rogawski MA | β | 2000 | β |
| Modifications of seizure susceptibility in Drosophila. | Kuebler D et al. | β | 2000 | β |
| Mutation analysis of the inwardly rectifying K(+) channels KCNJ6 (GIRK2) and KCNJ3 (GIRK1) in juvenile myoclonic epilepsy. | Hallmann K et al. | β | 2000 | β |
| No evidence for association between the KCNQ3 gene and susceptibility to idiopathic generalized epilepsy. | Haug K et al. | β | 2000 | β |
| Altered expression levels of G protein subclass mRNAs in various seizure stages of the kindling model. | Iwasa H et al. | β | 1999 | β |
| Benign familial neonatal epilepsy with mutations in two potassium channel genes. | Leppert M et al. | β | 1999 | β |
| Cesium induces spontaneous epileptiform activity without changing extracellular potassium regulation in rat hippocampus. | Xiong ZQ et al. | β | 1999 | β |
| Channelopathies of inwardly rectifying potassium channels. | Abraham MR et al. | β | 1999 | β |
| Characterization of G-protein-gated K+ channels composed of Kir3.2 subunits in dopaminergic neurons of the substantia nigra. | Inanobe A et al. | β | 1999 | β |
| Ethanol actions on multiple ion channels: which are important? | Harris RA | β | 1999 | β |
| Ethanol opens G-protein-activated inwardly rectifying K+ channels. | Kobayashi T et al. | β | 1999 | β |
| GIRK4 confers appropriate processing and cell surface localization to G-protein-gated potassium channels. | Kennedy ME et al. | β | 1999 | β |
| G protein gated potassium channels. | Sui JL et al. | β | 1999 | β |
| Ion channels and the genetic contribution to epilepsy. | Ryan SG | β | 1999 | β |
| Isolation and analysis of chromosome 21 genes potentially involved in Down syndrome. | Gosset P et al. | β | 1999 | β |
| Length variation of a polyglutamine array in the gene encoding a small-conductance, calcium-activated potassium channel (hKCa3) and susceptibility to idiopathic generalized epilepsy. | Sander T et al. | β | 1999 | β |
| Molecular cloning and characterization of a novel splicing variant of the Kir3.2 subunit predominantly expressed in mouse testis. | Inanobe A et al. | β | 1999 | β |
| Molecular manipulations as tools for enhancing our understanding of 5-HT neurotransmission. | Murphy DL et al. | β | 1999 | β |
| Recent advances in the genetics of epilepsy: insights from human and animal studies. | Prasad AN et al. | β | 1999 | β |
| Rescue of cerebellar granule cells from death in weaver NR1 double mutants. | Jensen P et al. | β | 1999 | β |
| The impact of genomics on mammalian neurobiology. | Hochgeschwender U et al. | β | 1999 | β |
| The weaver mouse gain-of-function phenotype of dopaminergic midbrain neurons is determined by coactivation of wvGirk2 and K-ATP channels. | Liss B et al. | β | 1999 | β |
| Weaver cerebellar granule neurons show altered expression of NMDA receptor subunits both in vivo and in vitro. | Liesi P et al. | β | 1999 | β |
| Abnormal heart rate regulation in GIRK4 knockout mice. | Wickman K et al. | β | 1998 | β |
| A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. | Singh NA et al. | β | 1998 | β |
| GABAB receptors: drugs meet clones. | Bettler B et al. | β | 1998 | β |
| Higher seizure susceptibility and enhanced tyrosine phosphorylation of N-methyl-D-aspartate receptor subunit 2B in fyn transgenic mice. | Kojima N et al. | β | 1998 | β |
| Identification of native atrial G-protein-regulated inwardly rectifying K+ (GIRK4) channel homomultimers. | Corey S et al. | β | 1998 | β |
| Mechanisms and experimental models of seizure generation. | Jefferys JG | β | 1998 | β |
| Pore mutation in a G-protein-gated inwardly rectifying K+ channel subunit causes loss of K+-dependent inhibition in weaver hippocampus. | Jarolimek W et al. | β | 1998 | β |
| Potassium ion channels and human disease: phenotypes to drug targets? | Curran ME | β | 1998 | β |
| Presynaptic receptors. | Miller RJ | β | 1998 | β |
| Using knockout and transgenic mice to study neurophysiology and behavior. | Picciotto MR et al. | β | 1998 | β |
| Activation of heteromeric G protein-gated inward rectifier K+ channels overexpressed by adenovirus gene transfer inhibits the excitability of hippocampal neurons. | Ehrengruber MU et al. | β | 1997 | β |
| Behavioral defects in C. elegans egl-36 mutants result from potassium channels shifted in voltage-dependence of activation. | Johnstone DB et al. | β | 1997 | β |
| Defective gamma-aminobutyric acid type B receptor-activated inwardly rectifying K+ currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice. | Slesinger PA et al. | β | 1997 | β |
| G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. | LΓΌscher C et al. | β | 1997 | β |
| Identification of regions that regulate the expression and activity of G protein-gated inward rectifier K+ channels in Xenopus oocytes. | Stevens EB et al. | β | 1997 | β |
| Ion channel mutations in mouse models of inherited neurological disease. | Meisler MH et al. | β | 1997 | β |
| Ontogeny of gene expression of Kir channel subunits in the rat. | Karschin C et al. | β | 1997 | β |
| Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. | Chouabe C et al. | β | 1997 | β |
| Voltage-gated and inwardly rectifying potassium channels. | Jan LY et al. | β | 1997 | β |