keyword
MENU ▼
Read by QxMD icon Read
search

Twik

keyword
https://www.readbyqxmd.com/read/28882594/terbinafine-is-a-novel-and-selective-activator-of-the-two-pore-domain-potassium-channel-task3
#1
Paul D Wright, Emma L Veale, David McCoull, David C Tickle, Jonathan M Large, Emma Ococks, Gemma Gothard, Catherine Kettleborough, Alistair Mathie, Jeffrey Jerman
Two-pore domain potassium channels (K2Ps) are characterized by their four transmembrane domain and two-pore topology. They carry background (or leak) potassium current in a variety of cell types. Despite a number of important roles there is currently a lack of pharmacological tools with which to further probe K2P function. We have developed a cell-based thallium flux assay, using baculovirus delivered TASK3 (TWIK-related acid-sensitive K(+) channel 3, KCNK9, K2P9.1) with the aim of identifying novel, selective TASK3 activators...
September 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28870160/trek-1-mediates-isoflurane-induced-cytotoxicity-in-astrocytes
#2
Haiyun Guo, Zhengwu Peng, Liu Yang, Xue Liu, Yaning Xie, Yanhui Cai, Lize Xiong, Yi Zeng
BACKGROUND: There are growing concerns that anaesthetic exposure can cause extensive apoptotic degeneration of neurons and the impairment of normal synaptic development and remodelling. However, little attention has been paid to exploring the possible cytotoxicity of inhalation anaesthetics, such as isoflurane, in astrocytes. In this research, we determined that prolonged exposure to an inhalation anaesthetic caused cytotoxicity in astrocytes, and we identified the underlying molecular mechanism responsible for this process...
September 5, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28830434/rational-confederation-of-genes-and-diseases-ngs-interpretation-via-genecards-malacards-and-varelect
#3
Noa Rappaport, Simon Fishilevich, Ron Nudel, Michal Twik, Frida Belinky, Inbar Plaschkes, Tsippi Iny Stein, Dana Cohen, Danit Oz-Levi, Marilyn Safran, Doron Lancet
BACKGROUND: A key challenge in the realm of human disease research is next generation sequencing (NGS) interpretation, whereby identified filtered variant-harboring genes are associated with a patient's disease phenotypes. This necessitates bioinformatics tools linked to comprehensive knowledgebases. The GeneCards suite databases, which include GeneCards (human genes), MalaCards (human diseases) and PathCards (human pathways) together with additional tools, are presented with the focus on MalaCards utility for NGS interpretation as well as for large scale bioinformatic analyses...
August 18, 2017: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28793254/a-soluble-fluorescent-binding-assay-reveals-pip2-antagonism-of-trek-1-channels
#4
Cerrone Cabanos, Miao Wang, Xianlin Han, Scott B Hansen
Lipid regulation of ion channels by low-abundance signaling lipids phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid (PA) has emerged as a central cellular mechanism for controlling ion channels and the excitability of nerves. A lack of robust assays suitable for facile detection of a lipid bound to a channel has hampered the probing of the lipid binding sites and measuring the pharmacology of putative lipid agonists for ion channels. Here, we show a fluorescent PIP2 competition assay for detergent-purified potassium channels, including TWIK-1-related K(+)-channel (TREK-1)...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28762161/muscarinic-receptors-in-adrenal-chromaffin-cells-physiological-role-and-regulation-of-ion-channels
#5
REVIEW
Masumi Inoue, Hidetada Matsuoka, Keita Harada, Lung-Sen Kao
Adrenal medullary chromaffin cells in mammals are innervated by sympathetic preganglionic nerve fibers, as are sympathetic ganglion neurons. Acetylcholine in the ganglion neurons is well established as mediating fast and slow excitatory postsynaptic potentials through nicotinic and muscarinic acetylcholine receptors (AChRs), respectively. The role of muscarinic AChRs during neuronal transmission in chromaffin cells varies among different mammals. Furthermore, the ion channel mechanisms associated with the muscarinic AChR-mediated increase in excitability of chromaffin cells are complicated and different from the excitation of ganglion neurons, which has been ascribed to the inhibition of M-type K(+) channels...
July 31, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28738160/atrial-selective-k-channel-blockers-potential-antiarrhythmic-drugs-in-atrial-fibrillation
#6
Ursula Ravens
In the wake of demographic change in Western countries atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. In this lecture, I will address drugs acting on potassium (K+) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles...
July 24, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28714121/acetylcholine-dependent-upregulation-of-task-1-channels-in-thalamic-interneurons-by-a-smooth-muscle-like-signalling-pathway
#7
Michael Leist, Susanne Rinné, Maia Datunashvili, Ania Aissaoui, Hans-Christian Pape, Niels Decher, Sven G Meuth, Thomas Budde
KEY POINTS: The ascending brainstem transmitter acetylcholine depolarizes thalamocortical relay neurons while it induces hyperpolarization in local circuit inhibitory interneurons. Sustained K(+) currents are modulated in thalamic neurons to control their activity modes; for the interneurons the molecular nature of the underlying ion channels is as yet unknown. Activation of TASK-1 K(+) channels results in hyperpolarization of interneurons and suppression of their action potential firing...
September 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28682878/the-involvement-of-potassium-channel-ork1-in-short-term-memory-and-sleep-in-drosophila
#8
Xiaoyan Zhang, Yabin Zheng, Qingguo Ren, Hong Zhou
BACKGROUND: The sleep and cognitive dysfunction are common in major depressive disorders (MDDs). Recently, the 2-pore domain potassium channel twik-related K(+) channel 1 (TREK-1) has been identified to be closely related to the etiology of MDD. However, whether TREK-1 is involved in the regulation of sleep and cognition is still unknown. METHODS: The present study tried to dissect the role of outwardly rectifying K+ channel-1 (ORK1) (TREK-1 homolog in Drosophila) in sleep and cognition in Drosophila...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28676394/the-glycine-hinge-of-transmembrane-segment-2-modulates-the-subcellular-localization-and-gating-properties-in-trek-channels
#9
Ren-Gong Zhuo, Peng Peng, Jian-Quan Zheng, Yun-Long Zhang, Lei Wen, Xiao-Li Wei, Xiao-Yun Ma
TWIK-Related K(+) channels (TREK), including TREK-1 and TREK-2, belong to the TREK/TRAAK subclass of two-pore domain K(+) (K2P) family. The important functions of transmembrane segment 4 (M4)-glycine hinge in TREK channel gating have been characterized, but the roles of M2-hinge (the equivalent residue of M4-hinge) remain unclear. Here, by characterizing the macroscopic currents, subcellular localization and gating properties of their M2-hinge mutants (G166A for TREK-1 and G196A for TREK-2), we investigated the functions of M2-hinge...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28605766/genehancer-genome-wide-integration-of-enhancers-and-target-genes-in-genecards
#10
Simon Fishilevich, Ron Nudel, Noa Rappaport, Rotem Hadar, Inbar Plaschkes, Tsippi Iny Stein, Naomi Rosen, Asher Kohn, Michal Twik, Marilyn Safran, Doron Lancet, Dana Cohen
A major challenge in understanding gene regulation is the unequivocal identification of enhancer elements and uncovering their connections to genes. We present GeneHancer, a novel database of human enhancers and their inferred target genes, in the framework of GeneCards. First, we integrated a total of 434 000 reported enhancers from four different genome-wide databases: the Encyclopedia of DNA Elements (ENCODE), the Ensembl regulatory build, the functional annotation of the mammalian genome (FANTOM) project and the VISTA Enhancer Browser...
January 1, 2017: Database: the Journal of Biological Databases and Curation
https://www.readbyqxmd.com/read/28443635/expression-and-localisation-of-two-pore-domain-k2p-background-leak-potassium-ion-channels-in-the-mouse-retina
#11
Steven Hughes, Russell G Foster, Stuart N Peirson, Mark W Hankins
Two-pore domain (K2P) potassium channels perform essential roles in neuronal function. These channels produce background leak type potassium currents that act to regulate resting membrane potential and levels of cellular excitability. 15 different K2P channels have been identified in mammals and these channels perform important roles in a wide number of physiological systems. However, to date there is only limited data available concerning the expression and role of K2P channels in the retina. In this study we conduct the first comprehensive study of K2P channel expression in the retina...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28419410/selective-and-state-dependent-activation-of-tresk-k2p-18-1-background-potassium-channel-by-cloxyquin
#12
Miklós Lengyel, Alice Dobolyi, Gábor Czirják, Péter Enyedi
BACKGROUND AND PURPOSE: Cloxyquin (5-cloroquinolin-8-ol) has been described as an activator of TRESK (K2P 18.1, TWIK-related spinal cord K(+) channel) background potassium channel. We have examined the specificity of the drug by testing several K2P channels. We have investigated the mechanism of cloxyquin-mediated TRESK activation, focusing on the differences between the physiologically relevant regulatory states of the channel. EXPERIMENTAL APPROACH: Potassium currents were measured by two-electrode voltage clamp in Xenopus oocytes and by whole-cell patch clamp in mouse dorsal root ganglion (DRG) neurons...
July 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28270749/identifying-candidate-genes-that-underlie-cellular-ph-sensitivity-in-serotonin-neurons-using-transcriptomics-a-potential-role-for-kir5-1-channels
#13
Madeleine M Puissant, Gary C Mouradian, Pengyuan Liu, Matthew R Hodges
Ventilation is continuously adjusted by a neural network to maintain blood gases and pH. Acute CO2 and/or pH regulation requires neural feedback from brainstem cells that encode CO2/pH to modulate ventilation, including but not limited to brainstem serotonin (5-HT) neurons. Brainstem 5-HT neurons modulate ventilation and are stimulated by hypercapnic acidosis, the sensitivity of which increases with increasing postnatal age. The proper function of brainstem 5-HT neurons, particularly during post-natal development is critical given that multiple abnormalities in the 5-HT system have been identified in victims of Sudden Infant Death Syndrome...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28160200/reversal-of-tresk-downregulation-alleviates-neuropathic-pain-by-inhibiting-activation-of-gliocytes-in-the-spinal-cord
#14
Jun Zhou, Hongtao Chen, Chengxiang Yang, Jiying Zhong, Wanyou He, Qingming Xiong
Despite the consensus that activation of TWIK-related spinal cord K(+) (TRESK) might contribute to the pathogenesis of chronic pain, the specific mechanisms underlying the transfer and development of pain signals still remain obscure. In the present study, we validated that TRESK was expressed in neurons instead of glial cells. Furthermore, in the SNI model of neuropathic pain (NP), downregulation of TRESK in spinal cord neurons resulted in upregulation of connexin 36 (Cx36) and connexin 43 (Cx43), both being subtypes of gap junctions in the spinal cord, with gliocytes in the spinal cord activated ultimately...
February 3, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28051863/development-of-the-first-two-pore-domain-potassium-channel-twik-related-k-channel-1-selective-agonist-possessing-in-vivo-antinociceptive-activity
#15
Delphine Vivier, Ismail Ben Soussia, Nuno Rodrigues, Stéphane Lolignier, Maïly Devilliers, Franck C Chatelain, Laetitia Prival, Eric Chapuy, Geoffrey Bourdier, Khalil Bennis, Florian Lesage, Alain Eschalier, Jérôme Busserolles, Sylvie Ducki
The TWIK-related K(+) channel, TREK-1, has recently emerged as an attractive therapeutic target for the development of a novel class of analgesic drugs, suggesting that activation of TREK-1 could result in pain inhibition. Here, we report the synthesis of a series of substituted acrylic acids (1-54) based on our previous work with caffeate esters. The analogues were evaluated for their ability to modulate TREK-1 channel by electrophysiology and for their in vivo antinociceptive activity (acetic acid-induced writhing and hot plate assays), leading to the identification of a series of novel molecules able to activate TREK-1 and displaying potent antinociceptive activity in vivo...
February 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27899610/malacards-an-amalgamated-human-disease-compendium-with-diverse-clinical-and-genetic-annotation-and-structured-search
#16
Noa Rappaport, Michal Twik, Inbar Plaschkes, Ron Nudel, Tsippi Iny Stein, Jacob Levitt, Moran Gershoni, C Paul Morrey, Marilyn Safran, Doron Lancet
The MalaCards human disease database (http://www.malacards.org/) is an integrated compendium of annotated diseases mined from 68 data sources. MalaCards has a web card for each of ∼20 000 disease entries, in six global categories. It portrays a broad array of annotation topics in 15 sections, including Summaries, Symptoms, Anatomical Context, Drugs, Genetic Tests, Variations and Publications. The Aliases and Classifications section reflects an algorithm for disease name integration across often-conflicting sources, providing effective annotation consolidation...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27850640/1002-increased-vasoreactivity-contributes-to-pulmonary-hypertension-in-the-twik-2-knockout-mouse
#17
Melanie Kitagawa, David Durgan, Julia Reynolds, Robert Bryan, Lavannya Pandit
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27826228/potentiation-of-schaffer-collateral-ca1-synaptic-transmission-by-eef2k-and-p38-mapk-mediated-mechanisms
#18
Weiguang Weng, Ying Chen, Man Wang, Yinghan Zhuang, Thomas Behnisch
The elongation factor 2 kinase (eEF2K), likewise known as CaMKIII, has been demonstrated to be involved in antidepressant responses of NMDA receptor antagonists. Even so, it remains open whether direct inhibition of eEF2K without altering up-stream or other signaling pathways affects hippocampal synaptic transmission and neuronal network synchrony. Inhibition of eEF2K by the selective and potent eEF2K inhibitor A-484954 induced a fast pre-synaptically mediated enhancement of synaptic transmission and synchronization of neural network activity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27765191/pitx2-modulates-atrial-membrane-potential-and-the-antiarrhythmic-effects%C3%A2-of%C3%A2-sodium-channel-blockers
#19
Fahima Syeda, Andrew P Holmes, Ting Y Yu, Samantha Tull, Stefan Michael Kuhlmann, Davor Pavlovic, Daniel Betney, Genna Riley, Jan P Kucera, Florian Jousset, Joris R de Groot, Stephan Rohr, Nigel A Brown, Larissa Fabritz, Paulus Kirchhof
BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs...
October 25, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27742566/atrial-fibrillation-therapeutic-potential-of-atrial-k-channel-blockers
#20
REVIEW
Ursula Ravens, Katja E Odening
Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K(+)) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets...
August 2017: Pharmacology & Therapeutics
keyword
keyword
100105
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"