Reference Database

Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations.
Stadler, Konstantin
Bierwirth, Claudia
Stoenica, Luminita
Battefeld, Arne
Reetz, Olivia
Mix, Eilhard
Schuchmann, Sebastian
Velmans, Tanja
Rosenberger, Karen
Bräuer, Anja U
Lehnardt, Seija
Nitsch, Robert
Budt, Matthias
Wolff, Thorsten
Kole, Maarten H P
Strauss, Ulf
Cerebral cortex (New York, N.Y. : 1991) 2014 Jan;24: 199-210

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-β 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.

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