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https://www.readbyqxmd.com/read/28377218/synergistic-activation-of-g-protein-gated-inwardly-rectifying-potassium-channels-by-cholesterol-and-pi-4-5-p2
#1
Anna N Bukiya, Avia Rosenhouse-Dantsker
G-protein gated inwardly rectifying potassium (GIRK or Kir3 or KACh) 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. In contrast to many other channels that are inhibited by cholesterol, the activity of the heterotetramer Kir3.1/Kir3.4 that underlies KACh in the heart is enhanced by cholesterol. Similarly, the activities of both the Kir3.4 homomer and its active pore mutant Kir3.4* (Kir3.4_S143T) are enhanced by cholesterol...
April 1, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27714763/amiselimod-a-novel-sphingosine-1-phosphate-receptor-1-modulator-has-potent-therapeutic-efficacy-for-autoimmune-diseases-with-low-bradycardia-risk
#15
Kunio Sugahara, Yasuhiro Maeda, Kyoko Shimano, Akira Mogami, Hirotoshi Kataoka, Kei Ogawa, Kumiko Hikida, Hiroshi Kumagai, Mahoko Asayama, Toshinobu Yamamoto, Tomohiko Harada, Pingping Ni, Shinsuke Inoue, Atsuhiro Kawaguchi
BACKGROUND AND PURPOSE: We conducted preclinical and clinical studies to examine the pharmacological, particularly cardiac, effects of amiselimod (MT-1303), a second-generation sphingosine 1-phosphate (S1P) receptor modulator, designed to reduce the bradycardia associated with fingolimod and other S1P receptor modulators. EXPERIMENTAL APPROACH: The selectivity of the active metabolite amiselimod phosphate (amiselimod-P) for human S1P receptors and activation of G-protein-coupled inwardly rectifying K(+) (GIRK) channels in human atrial myocytes were assessed...
January 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27713687/differential-effects-of-toluene-and-ethanol-on-dopaminergic-neurons-of-the-ventral-tegmental-area
#16
Sudarat Nimitvilai, Chang You, Devinder S Arora, Maureen A McElvain, Bertha J Vandegrift, Mark S Brodie, John J Woodward
Drugs of abuse increase the activity of dopaminergic neurons of the ventral tegmental area (VTA), and output from the VTA is critical for both natural and drug-induced reward and reinforcement. Ethanol and the abused inhalant toluene both enhance VTA neuronal firing, but the mechanisms of this effect is not fully known. In this study, we used extracellular recordings to compare the actions of toluene and ethanol on DA VTA neurons. Both ethanol and toluene increased the firing rate of DA neurons, although toluene was ~100 times more potent than ethanol...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27681124/acute-simian-varicella-virus-infection-causes-robust-and-sustained-changes-in-gene-expression-in-the-sensory-ganglia
#17
Nicole Arnold, Thomas Girke, Suhas Sureshchandra, Ilhem Messaoudi
Primary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100...
December 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27677639/genomic-and-functional-analysis-of-the-host-response-to-acute-simian-varicella-infection-in-the-lung
#18
Nicole Arnold, Thomas Girke, Suhas Sureshchandra, Christina Nguyen, Maham Rais, Ilhem Messaoudi
Varicella Zoster Virus (VZV) is the causative agent of varicella and herpes zoster. Although it is well established that VZV is transmitted via the respiratory route, the host-pathogen interactions during acute VZV infection in the lungs remain poorly understood due to limited access to clinical samples. To address these gaps in our knowledge, we leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related Simian Varicella Virus (SVV). Acute infection is characterized by immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity, and a down-regulation of genes involved in lung development...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27650223/systempiper-ngs-workflow-and-report-generation-environment
#19
Tyler W H Backman, Thomas Girke
BACKGROUND: Next-generation sequencing (NGS) has revolutionized how research is carried out in many areas of biology and medicine. However, the analysis of NGS data remains a major obstacle to the efficient utilization of the technology, as it requires complex multi-step processing of big data demanding considerable computational expertise from users. While substantial effort has been invested on the development of software dedicated to the individual analysis steps of NGS experiments, insufficient resources are currently available for integrating the individual software components within the widely used R/Bioconductor environment into automated workflows capable of running the analysis of most types of NGS applications from start-to-finish in a time-efficient and reproducible manner...
September 20, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27641604/the-questionnaire-on-autonomic-regulation-a-useful-concept-for-integrative-medicine
#20
REVIEW
Matthias Kröz, Marcus Reif, Danilo Pranga, Roland Zerm, Friedemann Schad, Erik Wim Baars, Matthias Girke
The concept of autonomic regulation (aR) reflects the relevance of the function of different autonomic systems for health. aR can be captured by questionnaires. We differentiate between a trait or constitutional aR questionnaire version including 12 (short-version) or 18 items, respectively, with three subscales (orthostatic-circulatory, rest/activity and digestive regulation), and an 18-item state aR questionnaire on the preceding week with four subscales (rest/activity, orthostatic-circulatory, thermo- and digestive regulation)...
September 2016: Journal of Integrative Medicine
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