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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels mediate the hyperpolarization-activated current I(h) and thus play important roles in the regulation of brain excitability. The subcellular distribution pattern of the HCN channels influences the effects that they exert on the properties and activity of neurons. However, little is known about the mechanisms that control HCN channel trafficking to subcellular compartments or that regulate their surface expression. Here we studied the dynamics of HCN channel trafficking in hippocampal neurons using dissociated cultures coupled with time lapse imaging of fluorophore-fused HCN channels. HCN1-green fluorescence protein (HCN1-GFP) channels resided in vesicle-like organelles that moved in distinct patterns along neuronal dendrites, and these properties were isoform-specific. HCN1 trafficking required intact actin and tubulin and was rapidly inhibited by activation of either NMDA or AMPA-type ionotropic glutamate receptors in a calcium-dependent manner. Glutamate-induced inhibition of the movement of HCN1-GFP-expressing puncta was associated with increased surface expression of both native and transfected HCN1 channels, and this surface expression was accompanied by augmented I(h). Taken together, the results reveal the highly dynamic nature of HCN1 channel trafficking in hippocampal neurons and provide a novel potential mechanism for rapid regulation of I(h), and hence of neuronal properties, via alterations of HCN1 trafficking and surface expression.

In this paper an original numerical model, based on the standard Berg model, is used to simulate the growth mechanism of Ti-doped VOx deposited with changing oxygen flow during reactive sputtering deposition. Ti-doped VOx thin films are deposited using a V target with Ti inserts. The effects of titanium inserts on the discharge voltage, deposition rate, and the ratio of V/Ti are investigated. By doping titanium in the vanadium target, the average sputtering yield decreases. In this case, the sputter erosion reduces, which is accompanied by a reduction in the deposition rate. The ratio between V content and Ti content in the film is measured using energy-dispersive x-ray spectroscopy (EDX). A decrease in the vanadium concentration with the increasing of the oxygen flow rate is detected using EDX. Results show a reasonable agreement between numerical and experimental data. [ABSTRACT FROM AUTHOR]