Search results for "Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels"

showing 5 items of 5 documents

Cannabinoid Control of Learning and Memory through HCN Channels

2016

The mechanisms underlying the effects of cannabinoids on cognitive processes are not understood. Here we show that cannabinoid type-1 receptors (CB1Rs) control hippocampal synaptic plasticity and spatial memory through the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that underlie the h-current (Ih), a key regulator of dendritic excitability. The CB1R-HCN pathway, involving c-Jun-N-terminal kinases (JNKs), nitric oxide synthase, and intracellular cGMP, exerts a tonic enhancement of Ih selectively in pyramidal cells located in the superficial portion of the CA1 pyramidal cell layer, whereas it is absent from deep-layer cells. Activation of the CB1R-HCN pathway impairs d…

0301 basic medicineMAP Kinase Kinase 4medicine.medical_treatmentMorpholinesNeuroscience(all)RegulatorMice TransgenicBiologyNaphthalenesHippocampusBiophysical PhenomenaArticleMembrane Potentials03 medical and health sciencesMice0302 clinical medicineReceptor Cannabinoid CB1medicineHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsAnimalsEnzyme InhibitorsReceptorCyclic GMPSpatial MemoryMembrane potentialNeuronsGeneral NeuroscienceLong-term potentiationDendritesSynaptic PotentialsCalcium Channel BlockersBenzoxazines030104 developmental biologyMutationExcitatory postsynaptic potentialCannabinoidSignal transductionNitric Oxide SynthaseNeuroscience030217 neurology & neurosurgeryIntracellularSignal TransductionNeuron
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HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond

2018

International audience; Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control neuronal excitability and their dysfunction has been linked to epileptogenesis but few individuals with neurological disorders related to variants altering HCN channels have been reported so far. In 2014, we described five individuals with epileptic encephalopathy due to de novo HCN1 variants. To delineate HCN1-related disorders and investigate genotype-phenotype correlations further, we assembled a cohort of 33 unpublished patients with novel pathogenic or likely pathogenic variants: 19 probands carrying 14 different de novo mutations and four families with dominantly inherited variants segre…

0301 basic medicineProbandMaleModels MolecularPotassium Channels[SDV]Life Sciences [q-bio]Medizinmedicine.disease_causeEpileptogenesisMembrane PotentialsEpilepsy0302 clinical medicineHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMissense mutationChildGeneticsMutationMiddle AgedPhenotype3. Good healthTransmembrane domainclinical spectrum; epilepsy; HCN1; intellectual disability; ion channelintellectual disabilityChild PreschoolEpilepsy GeneralizedFemaleSpasms InfantileAdultAdolescentCHO CellsBiology03 medical and health sciencesYoung AdultCricetulusHCN1medicineAnimalsHumansGeneralized epilepsyGenetic Association StudiesAgedInfantmedicine.diseaseElectric Stimulationclinical spectrum030104 developmental biologyMutationion channelMutagenesis Site-DirectedepilepsyNeurology (clinical)030217 neurology & neurosurgery
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Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations

2014

Central nervous system (CNS) inflammation involves the generation of inducible cytokines such as interferons (IFNs) and alterations in brain activity, yet the interplay of both is not well understood. Here, we show that in vivo elevation of IFNs by viral brain infection reduced hyperpolarization-activated currents (Ih) in cortical pyramidal neurons. In rodent brain slices directly exposed to type I IFNs, the hyperpolarization-activated cyclic nucleotide (HCN)-gated channel subunit HCN1 was specifically affected. The effect required an intact type I receptor (IFNAR) signaling cascade. Consistent with Ih inhibition, IFNs hyperpolarized the resting membrane potential, shifted the resonance fre…

MalePatch-Clamp TechniquesPotassium Channelsmedicine.medical_treatmentNeocortexInbred C57BLchemistry.chemical_compoundMiceReceptorsHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsReceptors InterferonMembrane potentialCerebral CortexNeuronsBlottingElectroencephalographyImmunohistochemistryCytokinemedicine.anatomical_structureInterferon Type IInterferonCytokinesSignal transductionWesternmedicine.drugSignal TransductionCognitive NeuroscienceCentral nervous systemBlotting WesternElectrophysiological ProcessesBiologyReal-Time Polymerase Chain ReactionTransfectionCellular and Molecular NeuroscienceCyclic nucleotidemedicineAnimalsHumansComputer SimulationIon channelNeuroinflammationInterferon-betaElectrophysiological PhenomenaRatsMice Inbred C57BLHEK293 CellschemistryNerve NetNeuroscienceInterferon type I
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Postsynaptic NO/cGMP Increases NMDA Receptor Currents via Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in the Hippocampus

2013

The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling cascade participates in the modulation of synaptic transmission. The effects of NO are mediated by the NO-sensitive cGMP-forming guanylyl cyclases (NO-GCs), which exist in 2 isoforms with indistinguishable regulatory properties. The lack of long-term potentiation (LTP) in knock-out (KO) mice deficient in either one of the NO-GC isoforms indicates the contribution of both NO-GCs to LTP. Recently, we showed that the NO-GC1 isoform is located presynaptically in glutamatergic neurons and increases the glutamate release via hyperpolarization-activated cyclic nucleotide (HCN)-gated channels in the hippocampus. Electrophysiologi…

Patch-Clamp TechniquesCognitive NeuroscienceLong-Term PotentiationIn Vitro TechniquesNeurotransmissionNitric OxideReceptors N-Methyl-D-AspartateMiceCellular and Molecular Neurosciencechemistry.chemical_compoundCyclic nucleotidePostsynaptic potentialHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsHCN channelAnimalsAnesthetics LocalCA1 Region HippocampalCyclic GMPCyclic guanosine monophosphateMice KnockoutNeuronsbiologyLidocaineTetraethylammoniumLong-term potentiationHyperpolarization (biology)Electric StimulationPyrimidinesAnimals Newbornnervous systemchemistryGuanylate CyclaseBiophysicsbiology.proteinNMDA receptorExcitatory Amino Acid AntagonistsNeuroscienceCerebral Cortex
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Cardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP.

2008

Important targets for cAMP signalling in the heart are hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels that underlie the depolarizing 'pacemaker' current, I(f). We studied the role of I(f) in mice, in which binding of cAMP to HCN4 channels was abolished by a single amino-acid exchange (R669Q). Homozygous HCN4(R669Q/R669Q) mice die during embryonic development. Prior to E12, homozygous and heterozygous embryos display reduced heart rates and show no or attenuated responses to catecholaminergic stimulation. Adult heterozygous mice display normal heart rates at rest and during exercise. However, following beta-adrenergic stimulation, hearts exhibit pauses and sino-atrial…

medicine.medical_specialtymedicine.medical_treatmentCyclic Nucleotide-Gated Cation ChannelsEmbryonic DevelopmentStimulationMice TransgenicBiologyIn Vitro TechniquesGeneral Biochemistry Genetics and Molecular BiologyCardiac pacemakerArticleMiceHeart RatePregnancyInternal medicineHeart ratemedicineCyclic AMPHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsAnimalsMyocytes CardiacMolecular BiologyIon channelCells CulturedCatecholaminergicGeneral Immunology and MicrobiologyGeneral NeuroscienceEmbryogenesisDepolarizationEmbryoHeartMice Inbred C57BLEndocrinologyMutationFemaleThe EMBO journal
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