ArticleProceedings of the National Academy of Sciences of the United States of America2014
Dual regulation of G proteins and the G-protein-activated K+ channels by lithium.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Barium and psoriasis: a mini-review and hypothesis linking environmental exposures to ion channel modulation.Frontiers in medicine · 2025Review
- Homeostasis to Allostasis: Prefrontal Astrocyte Roles in Cognitive Flexibility and Stress Biology.Advances in neurobiology · 2024Review
- Epilepsy in a mouse model of GNB1 encephalopathy arises from altered potassium (GIRK) channel signaling and is alleviated by a GIRK inhibitor.Frontiers in cellular neuroscience · 2023Article
- Modulation of GFrontiers in cellular neuroscience · 2022Article
- Differential acute impact of therapeutically effective and overdose concentrations of lithium on human neuronal single cell and network function.Translational psychiatry · 2021Article
- Review
- Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel.Nature communications · 2019Article
- Rare deleterious mutations are associated with disease in bipolar disorder families.Molecular psychiatry · 2017Article
- Chronic lithium treatment elicits its antimanic effects via BDNF-TrkB dependent synaptic downscaling.eLife · 2017Article
- Role of calcium channels in bipolar disorder.Current psychopharmacology · 2017Article
- Therapeutic Mechanisms of Lithium in Bipolar Disorder: Recent Advances and Current Understanding.CNS drugs · 2016Review
- Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons.Physiological reports · 2016Article
- Innovative approaches to bipolar disorder and its treatment.Annals of the New York Academy of Sciences · 2016Review
- Molecular neurobiological clues to the pathogenesis of bipolar disorder.Current opinion in neurobiology · 2016Review
- Brain oscillations in bipolar disorder and lithium-induced changes.Neuropsychiatric disease and treatment · 2016Review
- A Quantitative Model of the GIRK1/2 Channel Reveals That Its Basal and Evoked Activities Are Controlled by Unequal Stoichiometry of Gα and Gβγ.PLoS computational biology · 2015Article
- Differential effects of antidepressants escitalopram versus lithium on Gs alpha membrane relocalization.BMC neuroscience · 2015Article
- Modulation of GPCRs by monovalent cations and anions.Naunyn-Schmiedeberg's archives of pharmacology · 2015Review
- Recruitment of Gβγ controls the basal activity of G-protein coupled inwardly rectifying potassium (GIRK) channels: crucial role of distal C terminus of GIRK1.The Journal of physiology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Lithium (Li(+)) is widely used to treat bipolar disorder (BPD). Cellular targets of Li(+), such as glycogen synthase kinase 3β (GSK3β) and G proteins, have long been implicated in BPD etiology; however, recent genetic studies link BPD to other proteins, particularly ion channels. Li(+) affects neuronal excitability, but the underlying mechanisms and the relevance to putative BPD targets are unknown. We discovered a dual regulation of G protein-gated K(+) (GIRK) channels by Li(+), and identified the underlying molecular mechanisms. In hippocampal neurons, therapeutic doses of Li(+) (1-2 mM) increased GIRK basal current (Ibasal) but attenuated neurotransmitter-evoked GIRK currents (Ievoked) mediated by Gi/o-coupled G-protein-coupled receptors (GPCRs). Molecular mechanisms of these regulations were studied with heterologously expressed GIRK1/2. In excised membrane patches, Li(+) increased Ibasal but reduced GPCR-induced GIRK currents. Both regulations were membrane-delimited and G protein-dependent, requiring both Gα and Gβγ subunits. Li(+) did not impair direct activation of GIRK channels by Gβγ, suggesting that inhibition of Ievoked results from an action of Li(+) on Gα, probably through inhibition of GTP-GDP exchange. In direct binding studies, Li(+) promoted GPCR-independent dissociation of Gαi(GDP) from Gβγ by a Mg(2+)-independent mechanism. This previously unknown Li(+) action on G proteins explains the second effect of Li(+), the enhancement of GIRK's Ibasal. The dual effect of Li(+) on GIRK may profoundly regulate the inhibitory effects of neurotransmitters acting via GIRK channels. Our findings link between Li(+), neuronal excitability, and both cellular and genetic targets of BPD: GPCRs, G proteins, and ion channels.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.