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https://www.readbyqxmd.com/read/28526610/11-12-epoxyeicosatrienoic-acid-11-12-eet-reduces-excitability-and-excitatory-transmission-in-the-hippocampus
#1
Nandkishor K Mule, Anette C Orjuela Leon, John R Falck, Michael Arand, Anne Marowsky
Recent studies suggest a role for the arachidonic acid-derived epoxyeicosatrienoic acids (EETs) in attenuating epileptic seizures. However, their effect on neurotransmission has never been investigated in detail. Here, we studied how 11,12- and 14,15 EET affect excitability and excitatory neurotransmission in mouse hippocampus. 11,12 EET (2 μM), but not 14,15 EET (2 μM), induced the opening of a hyperpolarizing K(+) conductance in CA1 pyramidal cells. This action could be blocked by BaCl2, the G protein blocker GDPβ-S and the GIRK1/4 blocker tertiapin Q and the channel was thus identified as a GIRK channel...
May 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28487514/girk2-splice-variants-and-neuronal-g-protein-gated-k-channels-implications-for-channel-function-and-behavior
#2
Ezequiel Marron Fernandez de Velasco, Lei Zhang, Baovi N Vo, Megan Tipps, Shannon Farris, Zhilian Xia, Allison Anderson, Nicholas Carlblom, C David Weaver, Serena M Dudek, Kevin Wickman
Many neurotransmitters directly inhibit neurons by activating G protein-gated inwardly rectifying K(+) (GIRK) channels, thereby moderating the influence of excitatory input on neuronal excitability. While most neuronal GIRK channels are formed by GIRK1 and GIRK2 subunits, distinct GIRK2 isoforms generated by alternative splicing have been identified. Here, we compared the trafficking and function of two isoforms (GIRK2a and GIRK2c) expressed individually in hippocampal pyramidal neurons lacking GIRK2. GIRK2a and GIRK2c supported comparable somato-dendritic GIRK currents in Girk2 (-/-) pyramidal neurons, although GIRK2c achieved a more uniform subcellular distribution in pyramidal neurons and supported inhibitory postsynaptic currents in distal dendrites better than GIRK2a...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28472842/diterpene-lipo-alkaloids-with-selective-activities-on-cardiac-k-channels
#3
Tivadar Kiss, Botond Borcsa, Péter Orvos, László Tálosi, Judit Hohmann, Dezső Csupor
Aconitum diterpene alkaloids are known for their remarkable toxicity, which is due to their effect on ion channels. Activation of voltage-gated Na(+) channels is the major cause of their cardiotoxicity, however, influence on K(+) channels may also play a role in the overall effect.Here we report the synthesis of a series of lipo-alkaloids, including four new compounds, based on the 14-benzoylaconine structure, which is the core of a vast number of diterpene alkaloids naturally occurring in Aconitum species...
May 4, 2017: Planta Medica
https://www.readbyqxmd.com/read/28469002/neuropeptide-y-alters-vta-dopamine-neuron-activity-through-both-pre-and-post-synaptic-mechanisms
#4
Katherine Stuhrman West, Aaron G Roseberry
The mesocorticolimbic dopamine system, the brain's reward system, regulates many different behaviors including food intake, food reward, and feeding related behaviors, and there is increasing evidence that hypothalamic feeding-related neuropeptides alter dopamine neuron activity to affect feeding. For example, neuropeptide-Y (NPY), a strong orexigenic hypothalamic neuropeptide, increases motivation for food when injected into the ventral tegmental area (VTA). How NPY affects the activity of VTA dopamine neurons to regulate feeding behavior is unknown, however...
May 3, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28462392/mechanosensory-stimulation-evokes-acute-concussion-like-behavior-by-activating-girks-coupled-to-muscarinic-receptors-in-a-simple-vertebrate
#5
Wen-Chang Li, Xiao-Yue Zhu, Emma Ritson
Most vertebrates show concussion responses when their heads are hit suddenly by heavy objects. Previous studies have focused on the direct physical injuries to the neural tissue caused by the concussive blow. We study a similar behavior in a simple vertebrate, the Xenopus laevis tadpole. We find that concussion-like behavior can be reliably induced by the mechanosensory stimulation of the head skin without direct physical impacts on the brain. Head skin stimulation activates a cholinergic pathway which then opens G protein-coupled inward-rectifying potassium channels (GIRKs) via postsynaptic M2 muscarinic receptors to inhibit brainstem neurons critical for the initiation and maintenance of swimming for up to minutes and can explain many features commonly observed immediately after concussion...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28429525/induction-chemotherapy-ict-followed-by-radiochemotherapy-for-locally-advanced-head-and-neck-cancer-as-an-individual-treatment-approach-feasibility-safety-and-retrospective-survival-analysis-in-twenty-three-patients
#6
C-J Busch, J Girke, S Tribius, L Bussmann, R Knecht, P Schafhausen, B B Lörincz, A Münscher
Head and neck squamous cell carcinoma (HNSCC) patients with locoregionally advanced disease usually require multi-modality treatment including surgery, chemotherapy, and radiotherapy. Currently, cisplatin-based concurrent chemoradiation (CRT) remains the gold-standard for these patients [1]. Induction chemotherapy (ICT) prior to definitive therapy is regarded as an effective approach to shrink locally advanced disease allowing more effective and less toxic therapy, to select patients for organ preservation, to improve radiotherapy effectiveness, and also to potentially decrease the risk of distant metastasis due to initial systemic exposure [2]...
April 21, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28377218/synergistic-activation-of-g-protein-gated-inwardly-rectifying-potassium-channels-by-cholesterol-and-pi-4-5-p2
#7
Anna N Bukiya, Avia Rosenhouse-Dantsker
G-protein gated inwardly rectifying potassium (GIRK or Kir3) channels play a major role in the control of the heart rate, and require the membrane phospholipid phosphatidylinositol-bis-phosphate (PI(4,5)P2) for activation. Recently, we have shown that the activity of the heterotetrameric Kir3.1/Kir3.4 channel that underlies atrial KACh currents was enhanced by cholesterol. Similarly, the activities of both the Kir3.4 homomer and its active pore mutant Kir3.4* (Kir3.4_S143T) were also enhanced by cholesterol...
July 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28320163/inhibition-of-17-beta-estradiol-on-neuronal-excitability-via-enhancing-girk1-mediated-inwardly-rectifying-potassium-currents-and-girk1-expression
#8
Yuwen Zhang, Yian Huang, Guoxiang Wang, Xin Wang, Yun Wang
BACKGROUND: Catamenial epilepsy is a common central nervous system disease in female, which is influenced by the 17-β-estradiol (estrogen) level during the menstrual cycle. Low level (<0.05ng/ml) of estrogen normally accompanies with the perimenstrual classification of catamenial epilepsy, however, without clear mechanism. In previous studies, estrogen has been demonstrated to possess widely regulatory effects on potassium channels. Here, the effect of 17-β-estradiol on modulating inwardly rectifying K(+) (Kir) currents was investigated in cultured hippocampal neurons...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28253845/impact-of-a-combined-multimodal-aerobic-and-multimodal-intervention-compared-to-standard-aerobic-treatment-in-breast-cancer-survivors-with-chronic-cancer-related-fatigue-results-of-a-three-armed-pragmatic-trial-in-a-comprehensive-cohort-design
#9
Matthias Kröz, Marcus Reif, Augustina Glinz, Bettina Berger, Andreas Nikolaou, Roland Zerm, Benno Brinkhaus, Matthias Girke, Arndt Büssing, Christoph Gutenbrunner
BACKGROUND: Cancer-related fatigue (CRF) and insomnia are major complaints in breast cancer survivors (BC). Aerobic training (AT), the standard therapy for CRF in BC, shows only minor to moderate treatment effects. Other evidence-based treatments include cognitive behavioral therapy, e.g., sleep education/restriction (SE) and mindfulness-based therapies. We investigated the effectiveness of a 10-week multimodal program (MT) consisting of SE, psycho-education, eurythmy- and painting-therapy, administered separately or in combination with AT (CT) and compared both arms to AT alone...
March 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28223504/transcriptome-wide-microrna-and-target-dynamics-in-the-fat-body-during-the-gonadotrophic-cycle-of-aedes-aegypti
#10
Xiufeng Zhang, Emre Aksoy, Thomas Girke, Alexander S Raikhel, Fedor V Karginov
The mosquito Aedes aegypti is a major vector of numerous viral diseases, because it requires a blood meal to facilitate egg development. The fat body, a counterpart of mammalian liver and adipose tissues, is the metabolic center, playing a key role in reproduction. Therefore, understanding of regulatory networks controlling its functions is critical, and the role of microRNAs (miRNAs) in the process is largely unknown. We aimed to explore miRNA expression and potential targets in the female fat body of Ae. aegypti, as well as their changes postblood meal (PBM)...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28219978/a-mutation-in-the-g-protein-gene-gnb2-causes-familial-sinus-node-and-atrioventricular-conduction-dysfunction
#11
Birgit Stallmeyer, Johanna Kuß, Stefan Kotthoff, Sven Zumhagen, Kirsty S Vowinkel, Susanne Rinne, Lina A Matschke, Corinna Friedrich, Ellen Schulze-Bahr, Stephan Rust, Guiscard Seebohm, Niels Decher, Eric Schulze-Bahr
Rationale: Familial sinus node and atrioventricular (AV) conduction dysfunction is a rare disorder that leads to paroxysmal dizziness, fatigue and syncope due to a temporarily or permanent reduced heart rate. To date, only a few genes for familial sinus and/or AV conduction dysfunction are known and the majority of cases remain etiologically unresolved. Objective: We aim to identify the disease gene in a large three-generation family (n=25) with autosomal dominant sinus node dysfunction (SND) and AV block (AVB) and to characterise the mutation-related pathomechanisms in familial SND+AVB...
February 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28213520/cholesterol-up-regulates-neuronal-g-protein-gated-inwardly-rectifying-potassium-girk-channel-activity-in-the-hippocampus
#12
Anna N Bukiya, Serdar Durdagi, Sergei Noskov, Avia Rosenhouse-Dantsker
Hypercholesterolemia is a well known risk factor for the development of neurodegenerative disease. However, the underlying mechanisms are mostly unknown. In recent years, it has become increasingly evident that cholesterol-driven effects on physiology and pathophysiology derive from its ability to alter the function of a variety of membrane proteins including ion channels. Yet, the effect of cholesterol on G protein-gated inwardly rectifying potassium (GIRK) channels expressed in the brain is unknown. GIRK channels mediate the actions of inhibitory brain neurotransmitters...
April 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28196855/inactivation-of-girk-channels-weakens-the-pre-and-postsynaptic-inhibitory-activity-in-dorsal-raphe-neurons
#13
Nerea Llamosas, Luisa Ugedo, Maria Torrecilla
The serotonergic tone of the dorsal raphe (DR) is regulated by 5-HT1A receptors, which negatively control serotonergic activity via the activation of G protein-coupled inwardly rectifying K(+) (GIRK) channels. In addition, DR activity is modulated by local GABAergic transmission, which is believed to play a key role in the development of mood-related disorders. Here, we sought to characterize the role of GIRK2 subunit-containing channels on the basal electrophysiological properties of DR neurons and to investigate whether the presynaptic and postsynaptic activities of 5-HT1A, GABAB, and GABAA receptors are affected by Girk2 gene deletion...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28188005/g-protein-gated-potassium-channels-a-link-to-drug-addiction
#14
REVIEW
Robert A Rifkin, Stephen J Moss, Paul A Slesinger
G protein-gated inwardly rectifying potassium (GIRK) channels are regulators of neuronal excitability in the brain. Knockout mice lacking GIRK channels display altered behavioral responses to multiple addictive drugs, implicating GIRK channels in addictive behaviors. Here, we review the effects of GIRK subunit deletions on the behavioral response to psychostimulants, such as cocaine and methamphetamine. Additionally, exposure of mice to psychostimulants produces alterations in the surface expression of GIRK channels in multiple types of neurons within the reward system of the brain...
April 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28178331/large-scale-bioactivity-analysis-of-the-small-molecule-assayed-proteome
#15
Tyler William H Backman, Daniel S Evans, Thomas Girke
This study presents an analysis of the small molecule bioactivity profiles across large quantities of diverse protein families represented in PubChem BioAssay. We compared the bioactivity profiles of FDA approved drugs to non-FDA approved compounds, and report several distinct patterns characteristic of the approved drugs. We found that a large fraction of the previously reported higher target promiscuity among FDA approved compounds, compared to non-FDA approved bioactives, was frequently due to cross-reactivity within rather than across protein families...
2017: PloS One
https://www.readbyqxmd.com/read/28139680/ethanol-dependence-abolishes-monoamine-and-girk-kir3-channel-inhibition-of-orbitofrontal-cortex-excitability
#16
Sudarat Nimitvilai, Marcelo F Lopez, Patrick J Mulholland, John J Woodward
Alcohol abuse disorders are associated with dysfunction of frontal cortical areas including the orbitofrontal cortex (OFC). The OFC is extensively innervated by monoamines, and drugs that target monoamine receptors have been used to treat a number of neuropsychiatric diseases, including alcoholism. However, little is known regarding how monoamines affect OFC neuron excitability or whether this modulation is altered by chronic exposure to ethanol. In this study, we examined the effect of dopamine, norepinephrine, and serotonin on lateral OFC neuronal excitability in naive mice and in those exposed to chronic intermittent ethanol (CIE) treatment...
March 15, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28131769/suppression-of-inhibitory-g-protein-signaling-in-forebrain-pyramidal-neurons-triggers-plasticity-of-glutamatergic-neurotransmission-in-the-nucleus-accumbens-core
#17
Ezequiel Marron Fernandez de Velasco, Nicholas Carlblom, Zhilian Xia, Kevin Wickman
Cocaine and other drugs of abuse trigger long-lasting adaptations in excitatory and inhibitory neurotransmission in the mesocorticolimbic system, and this plasticity has been implicated in several key facets of drug addiction. For example, glutamatergic neurotransmission mediated by AMPA receptors (AMPAR) is strengthened in medium spiny neurons (MSNs) in the NAc core and shell during withdrawal following repeated in vivo cocaine administration. Repeated cocaine administration also suppresses inhibitory signaling mediated by G protein-gated inwardly rectifying K(+) (GIRK) channels in pyramidal neurons of the prelimbic cortex, an important source of glutamatergic input to the NAc core that has been implicated in cocaine-seeking and behavioral sensitization...
May 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28009293/calcium-release-from-stores-inhibits-girk
#18
Paul F Kramer, John T Williams
Synaptic transmission is mediated by ionotropic and metabotropic receptors that together regulate the rate and pattern of action potential firing. Metabotropic receptors can activate ion channels and modulate other receptors and channels. The present paper examines the interaction between group 1 mGluR-mediated calcium release from stores and GABAB/D2-mediated GIRK currents in rat dopamine neurons of the Substantia Nigra. Transient activation of mGluRs decreased the GIRK current evoked by GABAB and D2 receptors, although less efficaciously for D2...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27942993/diadenosine-pentaphosphate-affects-electrical-activity-in-guinea-pig-atrium-via-activation-of-potassium-acetylcholine-dependent-inward-rectifier
#19
Denis V Abramochkin, Viktoria M Karimova, Tatiana S Filatova, Andre Kamkin
Diadenosine pentaphosphate (Ap5A) belongs to the family of diadenosine polyphosphates, endogenously produced compounds that affect vascular tone and cardiac performance when released from platelets. The previous findings indicate that Ap5A shortens action potentials (APs) in rat myocardium via activation of purine P2 receptors. The present study demonstrates alternative mechanism of Ap5A electrophysiological effects found in guinea pig myocardium. Ap5A (10(-4) M) shortens APs in guinea pig working atrial myocardium and slows down pacemaker activity in the sinoatrial node...
December 10, 2016: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/27901161/optical-control-of-girk-channels-using-visible-light
#20
Julie B Trads, Jessica Burgstaller, Laura Laprell, David B Konrad, Luis de la Osa de la Rosa, C David Weaver, Herwig Baier, Dirk Trauner, David M Barber
G-protein coupled inwardly rectifying potassium (GIRK) channels are an integral part of inhibitory signal transduction pathways, reducing the activity of excitable cells via hyperpolarization. They play crucial roles in processes such as cardiac output, cognition and the coordination of movement. Therefore, the precision control of GIRK channels is of critical importance. Here, we describe the development of the azobenzene containing molecule VLOGO (Visible Light Operated GIRK channel Opener), which activates GIRK channels in the dark and is promptly deactivated when illuminated with green light...
December 20, 2016: Organic & Biomolecular Chemistry
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