6533b7defe1ef96bd1276814
RESEARCH PRODUCT
Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations
Robert NitschLuminita StoenicaClaudia BierwirthArne BattefeldOlivia ReetzKonstantin StadlerMatthias BudtKaren RosenbergerAnja U. BräuerEilhard MixSeija LehnardtThorsten WolffTanja VelmansSebastian SchuchmannUlf StraussMaarten H. P. Kolesubject
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 Idescription
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 frequency, and increased the membrane impedance. In vivo application of IFN-gamma to the rat and to the mouse cerebral cortex reduced the power of higher frequencies in the cortical electroencephalographic activity only in the presence of HCN1. In summary, these findings identify HCN1 channels as a novel neural target for type I IFNs providing the possibility to tune neural responses during the complex event of a CNS inflammation
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 |