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https://www.readbyqxmd.com/read/29763576/g-i-protein-functions-in-thalamic-neurons-to-decrease-orofacial-nociceptive-response
#1
Jennifer Strand, Crystal Stinson, Larry L Bellinger, Yuan Peng, Phillip R Kramer
Orofacial pain includes neuronal pathways that project from the trigeminal nucleus to and through the thalamus. What role the ventroposterior thalamic complex (VP) has on orofacial pain transmission is not understood. To begin to address this question an inhibitory G protein (Gi) designer receptor exclusively activated by a designer drug (DREADD) was transfected in cells of the VP using adeno-associated virus isotype 8. Virus infected cells were identified by a fluorescent tag and immunostaining. Cells were silenced after injecting the designer drug clozapine-n-oxide, which binds the designer receptor activating Gi ...
May 12, 2018: Brain Research
https://www.readbyqxmd.com/read/29730318/a-real-time-screening-assay-for-cannabinoid-cb1-receptor-mediated-signaling
#2
Haley K Andersen, Kenneth B Walsh
The cannabinoid CB1 receptor is expressed throughout the central nervous system where it functions to regulate neurotransmitter release and synaptic plasticity. While the CB1 receptor has been identified as a target for both natural and synthetic cannabinoids, the specific downstream signaling pathways activated by these various ligands have not been fully described. In this study, we developed a real-time membrane potential fluorescent assay for cannabinoids using pituitary AtT20 cells that endogenously express G protein-gated inward rectifier K+ (GIRK) channels and were stably transfected with the CB1 receptor using a recombinant lentivirus...
May 3, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29689260/effects-of-monoamines-on-the-intrinsic-excitability-of-lateral-orbitofrontal-cortex-neurons-in-alcohol-dependent-and-non-dependent-female-mice
#3
Sudarat Nimitvilai, Marcelo F Lopez, John J Woodward
Changes in brain reward and control systems of frontal cortical areas including the orbitofrontal cortex (OFC) are associated with alcohol use disorders (AUD). The OFC is extensively innervated by monoamines, and drugs that target monoamine receptors have been used to treat a number of neuropsychiatric diseases, including AUDs. Recent findings from this laboratory demonstrate that D2, α2-adrenergic and 5HT1A receptors all decrease the intrinsic excitability of lateral OFC (lOFC) neurons in naïve male mice and that this effect is lost in mice exposed to repeated cycles of chronic intermittent ethanol (CIE) vapor...
April 21, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29679681/inhibition-of-protein-kinase-a-and-girk-channel-reverses-fentanyl-induced-respiratory-depression
#4
Xiaonan Liang, Zheng Yong, Ruibin Su
Opioid-induced respiratory depression is a major obstacle to improving the clinical management of moderate to severe chronic pain. Opioids inhibit neuronal activity via various pathways, including calcium channels, adenylyl cyclase, and potassium channels. Currently, the underlying molecular pathway of opioid-induced respiratory depression is only partially understood. This study aimed to investigate the mechanisms of opioid-induced respiratory depression in vivo by examining the effects of different pharmacological agents on fentanyl-induced respiratory depression...
April 18, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29596449/sequence-analysis-of-the-potato-aphid-macrosiphum-euphorbiae-transcriptome-identified-two-new-viruses
#5
Marcella A Teixeira, Noa Sela, Hagop S Atamian, Ergude Bao, Ritu Chaudhary, Jacob MacWilliams, Jiangman He, Sophie Mantelin, Thomas Girke, Isgouhi Kaloshian
The potato aphid, Macrosiphum euphorbiae, is an important agricultural pest that causes economic losses to potato and tomato production. To establish the transcriptome for this aphid, RNA-Seq libraries constructed from aphids maintained on tomato plants were used in Illumina sequencing generating 52.6 million 75-105 bp paired-end reads. The reads were assembled using Velvet/Oases software with SEED preprocessing resulting in 22,137 contigs with an N50 value of 2,003bp. After removal of contigs from tomato host origin, 20,254 contigs were annotated using BLASTx searches against the non-redundant protein database from the National Center for Biotechnology Information (NCBI) as well as IntereProScan...
2018: PloS One
https://www.readbyqxmd.com/read/29581303/structural-basis-for-the-ethanol-action-on-g-protein-activated-inwardly-rectifying-potassium-channel-1-revealed-by-nmr-spectroscopy
#6
Yuki Toyama, Hanaho Kano, Yoko Mase, Mariko Yokogawa, Masanori Osawa, Ichio Shimada
Ethanol consumption leads to a wide range of pharmacological effects by acting on the signaling proteins in the human nervous system, such as ion channels. Despite its familiarity and biological importance, very little is known about the molecular mechanisms underlying the ethanol action, due to extremely weak binding affinity and the dynamic nature of the ethanol interaction. In this research, we focused on the primary in vivo target of ethanol, G-protein-activated inwardly rectifying potassium channel (GIRK), which is responsible for the ethanol-induced analgesia...
April 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29499411/girk1-mediated-inwardly-rectifying-potassium-current-suppresses-the-epileptiform-burst-activities-and-the-potential-antiepileptic-effect-of-ml297
#7
Yian Huang, Yuwen Zhang, Shuzhen Kong, Kai Zang, Shize Jiang, Li Wan, Lulan Chen, Guoxiang Wang, Min Jiang, Xin Wang, Jie Hu, Yun Wang
G protein-gated inwardly rectifying potassium (GIRK) channels are important inhibitory regulators of neuronal excitability in central nervous system, and the impairment of GIRK channel function has been reported to be associated with the susceptibility of epilepsy. However, the dynamics of GIRK channels in the pathogenesis of epilepsy are still unclear. In this study, our results showed that cyclothiazide, a potent convulsant, dose dependently increased the epileptiform bursting activities and suppressed the baclofen induced GIRK currents...
May 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29467578/cholesterol-binding-sites-in-girk-channels-the-devil-is-in-the-details
#8
Avia Rosenhouse-Dantsker
In recent years, it has become evident that cholesterol plays a direct role in the modulation of a variety of ion channels. In most cases, cholesterol downregulates channel activity. In contrast, our earlier studies have demonstrated that atrial G protein inwardly rectifying potassium (GIRK) channels are upregulated by cholesterol. Recently, we have shown that hippocampal GIRK currents are also upregulated by cholesterol. A combined computational-experimental approach pointed to putative cholesterol-binding sites in the transmembrane domain of the GIRK2 channel, the primary subunit in hippocampal GIRK channels...
2018: Lipid Insights
https://www.readbyqxmd.com/read/29443418/potential-roles-of-ycf54-and-ferredoxin-nadph-reductase-for-magnesium-protoporphyrin-monomethylester-cyclase
#9
Josephine Herbst, Annabel Girke, Mohammad Reza Hajirezaei, Guy Hanke, Bernhard Grimm
Chlorophyll is synthesized from activated glutamate in the tetrapyrrole biosynthesis pathway through at least 20 different enzymatic reactions. Among these, the MgProto monomethylester (MgProtoME) cyclase catalyzes the formation of a fifth isocyclic ring to tetrapyrroles to form protochlorophyllide. The enzyme consists of two proteins. The CHL27 protein is proposed to be the catalytic component, while LCAA/YCF54 likely acts as a scaffolding factor. In comparison to other reactions of chlorophyll biosynthesis, this enzymatic step lacks clear elucidation and it is hardly understood, how electrons are delivered for the NADPH-dependent cyclization reaction...
May 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29407764/rimonabant-a-potent-cb1-cannabinoid-receptor-antagonist-is-a-g%C3%AE-i-o-protein-inhibitor
#10
Alessandra Porcu, Miriam Melis, Rostislav Turecek, Celine Ullrich, Ignazia Mocci, Bernhard Bettler, Gian Luigi Gessa, M Paola Castelli
Rimonabant is a potent and selective cannabinoid CB1 receptor antagonist widely used in animal and clinical studies. Besides its antagonistic properties, numerous studies have shown that, at micromolar concentrations rimonabant behaves as an inverse agonist at CB1 receptors. The mechanism underpinning this activity is unclear. Here we show that micromolar concentrations of rimonabant inhibited Gαi/o -type G proteins, resulting in a receptor-independent block of G protein signaling. Accordingly, rimonabant decreased basal and agonist stimulated [35 S]GTPγS binding to cortical membranes of CB1- and GABAB -receptor KO mice and Chinese Hamster Ovary (CHO) cell membranes stably transfected with GABAB or D2 dopamine receptors...
May 1, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29374839/chronic-alcohol-intrinsic-excitability-and-potassium-channels-neuroadaptations-and-drinking-behavior
#11
Reginald Cannady, Jennifer A Rinker, Sudarat Nimitvilai, John J Woodward, Patrick J Mulholland
Neural mechanisms underlying alcohol use disorder remain elusive, and this lack of understanding has slowed the development of efficacious treatment strategies for reducing relapse rates and prolonging abstinence. While synaptic adaptations produced by chronic alcohol exposure have been extensively characterized in a variety of brain regions, changes in intrinsic excitability of critical projection neurons are understudied. Accumulating evidence suggests that prolonged alcohol drinking and alcohol dependence produce plasticity of intrinsic excitability as measured by changes in evoked action potential firing and after-hyperpolarization amplitude...
January 28, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29361487/novel-approach-for-in-vivo-detection-of-vulnerable-coronary-plaques-using-molecular-3-t-cmr-imaging-with-an-albumin-binding-probe
#12
Leif-Christopher Engel, Ulf Landmesser, Kevin Gigengack, Thomas Wurster, Constantina Manes, Georg Girke, Milosz Jaguszewski, Carsten Skurk, David M Leistner, Alexander Lauten, Andreas Schuster, Bernd Hamm, Rene M Botnar, Marcus R Makowski, Boris Bigalke
OBJECTIVES: This study sought to investigate the potential of the noninvasive albumin-binding probe gadofosveset-enhanced cardiac magnetic resonance (GE-CMR) for detection of coronary plaques that can cause acute coronary syndromes (ACS). BACKGROUND: ACS are frequently caused by rupture or erosion of coronary plaques that initially do not cause hemodynamically significant stenosis and are therefore not detected by invasive x-ray coronary angiography (XCA). METHODS: A total of 25 patients with ACS or symptoms of stable coronary artery disease underwent GE-CMR, clinically indicated XCA, and optical coherence tomography (OCT) within 24 h...
January 12, 2018: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/29352184/expression-and-relevance-of-the-g-protein-gated-k-channel-in-the-mouse-ventricle
#13
Allison Anderson, Kanchan Kulkarni, Ezequiel Marron Fernandez de Velasco, Nicholas Carlblom, Zhilian Xia, Atsushi Nakano, Kirill A Martemyanov, Elena G Tolkacheva, Kevin Wickman
The atrial G protein-gated inwardly rectifying K+ (GIRK) channel is a critical mediator of parasympathetic influence on cardiac physiology. Here, we probed the details and relevance of the GIRK channel in mouse ventricle. mRNAs for the atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscarinic receptor (M2 R), and RGS6, a negative regulator of atrial GIRK-dependent signaling, were detected in mouse ventricle at relatively low levels. The cholinergic agonist carbachol (CCh) activated small GIRK currents in adult wild-type ventricular myocytes that exhibited relatively slow kinetics and low CCh sensitivity; these currents were absent in ventricular myocytes from Girk1-/- or Girk4-/- mice...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29342363/differential-effects-of-inhibitory-g-protein-isoforms-on-g-protein-gated-inwardly-rectifying-k-currents-in-adult-murine-atria
#14
Muriel Nobles, David Montaigne, Sonia Sebastian, Lutz Birnbaumer, Andrew Tinker
G-protein gated inwardly rectifying K+ (GIRK) channels are the major inwardly rectifying K+ currents in cardiac atrial myocytes and an important determinant of atrial electrophysiology. Inhibitory G-protein alpha subunits can both mediate activation via acetylcholine but can also supress basal currents in the absence of agonist. We studied this phenomenon using whole cell patch clamping in murine atria from mice with global genetic deletion of Gαi2, combined deletion of Gαi1/Gαi3 and littermate controls...
January 17, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29341826/mu-opioid-receptors-inhibit-the-exercise-pressor-reflex-by-closing-n-type-calcium-channels-but-not-by-opening-girk-channels-in-rats
#15
Juan A Estrada, Marc P Kaufman
Mu opioid G-protein coupled receptors (MOR) interact with ion channels to decrease neuronal excitability. In humans, intrathecal administration of the MOR agonist, fentanyl, inhibits the exercise pressor reflex, an effect that can be attributed to either the opening of inward rectifying potassium channels (GIRK) or the closing of N-type calcium channels. The purpose of this study was to determine if the highly selective MOR agonist DAMGO attenuates the exercise pressor reflex, and which of these two channels are responsible for this effect...
January 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29305262/point-mutation-of-a-conserved-aspartate-d69-in-the-muscarinic-m-2-receptor-does-not-modify-voltage-sensitive-agonist-potency
#16
Richard Ågren, Kristoffer Sahlholm, Johanna Nilsson, Peter Århem
The muscarinic M2 receptor (M2 R) has been shown to display voltage-sensitive agonist binding, based on G protein-activated inward rectifier potassium channel (GIRK) opening and radioligand binding at different membrane voltages. A conserved aspartate in transmembrane segment (TM) II of M2 R, D69, has been proposed as the voltage sensor. While a recent paper instead presented evidence of tyrosines in TMs III, VI, and VII acting as voltage sensors, these authors were not able to record GIRK channel activation by a D69N mutant M2 R...
January 29, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29180115/deletion-of-girk2-subunit-containing-girk-channels-of-neurons-expressing-dopamine-transporter-decrease-immobility-time-on-forced-swimming-in-mice
#17
Ikutaro Honda, Kimi Araki, Sokichi Honda, Fumio Soeda, Min-Chul Shin, Shogo Misumi, Ken-Ichi Yamamura, Kazuo Takahama
We previously reported that non-narcotic antitussives possessing inhibitory actions on G protein-coupled inwardly rectifying potassium (GIRK) channels have antidepressant-like effects in the forced swimming test in normal and adrenocoticotropic hormone (ACTH) treated rats. Furthermore, the antidepressant-like effects of the antitussives such as tipepidine were blocked by dopamine D1 receptor antagonist, and inhibitory actions on GIRK channels of dopamine neurons may be involved in the antidepressant-like effects of tipepidine...
February 5, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29177691/differential-association-of-gaba-b-receptors-with-their-effector-ion-channels-in-purkinje-cells
#18
Rafael Luján, Carolina Aguado, Francisco Ciruela, Javier Cózar, David Kleindienst, Luis de la Ossa, Bernhard Bettler, Kevin Wickman, Masahiko Watanabe, Ryuichi Shigemoto, Yugo Fukazawa
Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines...
November 25, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29131436/gaba-b-receptors-in-neocortical-and-hippocampal-pyramidal-neurons-are-coupled-to-different-potassium-channels
#19
Jean-Didier Breton, Greg J Stuart
Classically, GABAB receptors are thought to regulate neuronal excitability via G-protein-coupled inwardly rectifying potassium (GIRK) channels. Recent data, however, indicate that GABAB receptors can also activate two-pore domain potassium channels. Here, we investigate which potassium channels are coupled to GABAB receptors in rat neocortical layer 5 and hippocampal CA1 pyramidal neurons. Bath application of the non-specific GIRK channel blocker barium (200 μm) abolished outward currents evoked by GABAB receptors in CA1 pyramidal, but only partially blocked GABAB responses in layer 5 neurons...
December 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29126768/increased-functional-coupling-of-5-ht-1a-autoreceptors-to-girk-channels-in-tph2-mice
#20
Boris Mlinar, Alberto Montalbano, Jonas Waider, Klaus-Peter Lesch, Renato Corradetti
Firing activity of serotonergic neurons is under regulatory control by somatodendritic 5-HT1A autoreceptors (5-HT1A ARs). Enhanced 5-HT1A AR functioning may cause decreased serotonergic signaling in brain and has thereby been implicated in the etiology of mood and anxiety disorders. Tryptophan hydroxylase-2 knockout (Tph2-/- ) mice exhibit sensitization of 5-HT1A agonist-induced inhibition of serotonergic neuron firing and thus represents a unique animal model of enhanced 5-HT1A AR functioning. To elucidate the mechanisms underlying 5-HT1A AR supersensitivity in Tph2-/- mice, we characterized the activation of G protein-coupled inwardly-rectifying potassium (GIRK) conductance by the 5-HT1A receptor agonist 5-carboxamidotryptamine using whole-cell recordings from serotonergic neurons in dorsal raphe nucleus...
December 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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