Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations.
Cerebral Cortex. 2012-10-04; 24(1): 199-210
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1. Cereb Cortex. 2014 Jan;24(1):199-210. doi: 10.1093/cercor/bhs305. Epub 2012 Oct
Elevation in type I interferons inhibits HCN1 and slows cortical neuronal
Stadler K(1), Bierwirth C, Stoenica L, Battefeld A, Reetz O, Mix E, Schuchmann S,
Velmans T, Rosenberger K, Bräuer AU, Lehnardt S, Nitsch R, Budt M, Wolff T, Kole
MH, Strauss U.
(1)Institute of Cell Biology and Neurobiology.
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.
PMID: 23042740 [Indexed for MEDLINE]