G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels: Molecular, cellular, and subcellular diversity.

G protein-gated inwardly rectifying K (GIRK/K3) channels are mainly expressed in excitable cells such as neurons and atrial myocytes, where they can respond to a wide variety of neurotransmitters. Four GIRK subunits have been found in mammals (GIRK1-4) and act as downstream targets for various Gαi/o-linked G protein-coupled receptors (GPCRs). Activation of GIRK channels produces a postsynaptic efflux of potassium from the cell, responsible for hyperpolarization/inhibition of the neuron.

Chronic ethanol exposure in mice evokes pre- and postsynaptic deficits in GABAergic transmission in ventral tegmental area GABA neurons.

Background And Purpose: GABAergic neurons in mouse ventral tegmental area (VTA) exhibit elevated activity during withdrawal following chronic ethanol exposure. While increased glutamatergic input and decreased GABA receptor sensitivity have been implicated, the impact of inhibitory signaling in VTA GABA neurons has not been fully addressed.

Experimental Approach: We used electrophysiological and ultrastructural approaches to assess the impact of chronic intermittent ethanol vapour exposure in mice on GABAergic transmission in VTA GABA neurons during withdrawal.

Amyloid-β oligomers trigger sex-dependent inhibition of GIRK channel activity in hippocampal neurons in mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by amyloid plaques and cognitive decline, the latter of which is thought to be driven by soluble oligomeric amyloid-β (oAβ). The dysregulation of G protein-gated inwardly rectifying K (GIRK; also known as Kir3) channels has been implicated in rodent models of AD. Here, seeking mechanistic insights, we uncovered a sex-dependent facet of GIRK-dependent signaling in AD-related amyloid pathophysiology.

Exchangeable copper for patients with Wilson disease at follow-up: Rethinking normal ranges or changing methodology.

Background And Aim: Determining suitable copper parameters for monitoring Wilson disease remains a topic of ongoing discussion. International recommendations currently rely on the combination of urinary copper excretion and nonspecific liver markers when considering therapy and time elapsed since diagnosis. The emergence of exchangeable copper (CuEX) as a novel measurement reflecting the "free copper pool" held promise as a valuable target to ensure metabolic stability during follow-up, although the validation of target ranges remains unknown.

Selective disruption of synaptic NMDA receptors of the hippocampal trisynaptic circuit in Aβ pathology.

Synaptic dysfunction is an early feature in Alzheimer's disease (AD) pathogenesis and a major morphological correlate of memory deficits. Given the main synaptic location of N-methyl-D-aspartate receptors (NMDARs), their dysregulation has been implicated in these pathological effects. Here, to detect possible alterations in the expression and synaptic localisation of the GluN1 subunit in the brain of amyloidogenic APP/PS1 mice, we employed histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques.